ПРОИЗВОДНЫЕ ИНДЕНА В КАЧЕСТВЕ ФАРМАЦЕВТИЧЕСКИХ СРЕДСТВ

Настоящее изобретение относится к соединениям формулы (I) в виде отдельного стереоизомера, смеси стереоизомеров или рацемической смеси стереоизомеров и их фармацевтически приемлемым солям. Соединения настоящего изобретения обладают противовоспалительной активностью. В формуле (I) ! ! кольцо А, С или D независимо является полностью или частично насыщенным; каждый из С1, С4, С11, С12, С15 и С16 независимо замещен двумя атомами водорода; каждый из С9 и С14 независимо замещен атомом водорода; R1 означает -OR7 или -N(R7)2. Значения остальных радикалов указаны в формуле изобретения. Изобретение также относится к фармацевтической композиции, обладающей противовоспалительной активностью и содержащей эффективное количество соединения изобретения, и к применению соединений для получения лекарственного средства, обладающего противовоспалительной активностью. 3 н. и 20 з.п. ф-лы.

СПОСОБ ПРИГОТОВЛЕНИЯ СОЛЕЙ КАРБОНОВОЙ КИСЛОТЫ, ОБЛАДАЮЩИХ ГЕРБИЦИДНЫМ ДЕЙСТВИЕМ

Изобретение относится к способу приготовления гербицидно активной соли карбоновой кислоты, который включает стадии: объединения карбоновой кислоты с высококипящим, не смешивающимся с водой органическим растворителем для получения раствора или суспензии; обработки полученного на стадии (i) раствора или суспензии основанием для образования соли карбоновой кислоты; удаления растворителя из полученной на стадии (ii) смеси для получения кека соли карбоновой кислоты; и iv) высушивания полученного на стадии (iii) кека. Изобретение также относится к способу изготовления дикамба-натрия, включающему стадии: растворения карбоновой кислоты, состоящей по существу из дикамбы, в высококипящем, не смешивающемся с водой инертном органическом растворителе для получения раствора или суспензии; обработки раствора или суспензии дикамбы со стадии (1) основанием, выбранным из гидроксида натрия, бикарбоната натрия и их смесей, в мольном соотношении 1 : 0,97 ±0,6% для образования дикамба-натрия; центрифугирования ...

ПРОЦЕСС ПОЛУЧЕНИЯ СОЕДИНЕНИЙ-ПРЕДШЕСТВЕННИКОВ ДЛЯ РАДИОАКТИВНЫХ ГАЛОГЕНПОМЕЧЕННЫХ СОЕДИНЕНИЙ

Изобретение относится к способу получения соединения -предшественника радиоактивного соединения, помеченного фтором, формулы (2), который включает: стадию взаимодействия, обеспечивающего условия для взаимодействия раствора, содержащего вещество со следующей химической формулой (I): где R1 обозначает защитную группу карбоксильной группы, a R2 - защитную группу аминогруппы вместе с основанием, выбранным из группы, состоящей из алкиламинов, от первичных до четвертичных, с неразветвленной или разветвленной цепью, с 1-10 атомами углерода, азотсодержащих гетероциклических веществ с 2-20 атомами углерода и азотсодержащих гетероароматических веществ с 2-20 атомами углерода, и соединением, реагирующим с ОН-группой соединения с химической формулой (1), с превращением в уходящую группу, выбранным из группы, состоящей из алкилсульфоновой кислоты с неразветвленной или разветвленной цепью из 1-10 атомов углерода, галоалкилсульфоновой кислоты с неразветвленной или разветвленной цепью из 1-9 атомов углерода ...

СОЕДИНЕНИЯ ДЛЯ НАЦЕЛЕННОЙ ДОСТАВКИ ЛЕКАРСТВЕННОГО СРЕДСТВА И УСИЛЕНИЯ АКТИВНОСТИ siPHK

Изобретение относится к соединениям формулы I, которые могут найти применение для улучшения доставки терапевтических лекарственных средств и усиления их активности. В формуле I Rи Rнезависимо выбираются из группы, состоящей из С-Салкильной, С-Салкенильной и олеильной группы; Rи Rнезависимо выбираются из группы, состоящей из С-Салкила и С-Салканола; X выбирается из группы, состоящей из -СН- и -S-, или отсутствует; Y выбирается из -(CH)и -S(CH), где n=1-4; а=1-4; b=1-4; с=1-4 и Z является противоионом. Изобретение относится также к специфичному к звездчатым клеткам носителю для лекарственного средства, содержащему специфичное к звездчатым клеткам количество молекулы ретиноида и катионного липида, состоящего из соединения формулы I. 2 н. и 29 з.п. ф-лы, 16 ил., 14 табл., 43 пр.

СПОСОБ ПОЛУЧЕНИЯ N-АЛКИЛ(ФЕНИЛ)-N,N-БИС[4-АЛКОКСИ(ФЕНОКСИ-, БЕНЗИЛОКСИ-, ПРОП-2-ИНИЛОКСИ)-2-БУТИНИЛ]АМИНОВ

Изобретение относится к новому способу получения новых N-алкил(фенил)-N,N-бис[4-алкокси(фенокси-, бензилокси- или проп-2-инилокси)-2-бутинил]аминов общей формулы (1).Соединения общей формулы (1) могут быть использованы в качестве универсальных прекурсоров для тонкого органического синтеза и биологически активных соединений. В общей формуле (1)Способ заключается в том, что N-алкил(фенил)-1,5,3-диоксазепан общей формулы RN(CHOCH)(где R= Ph, н-Bu, трет-Bu) подвергают взаимодействию с пропаргиловым эфиром общей формулы HC≡CCHOR, где R= трет-Bu, Ph, СНС≡СН, Bn, в присутствии катализатора CuCl при мольном соотношении N-алкил(фенил)-1,5,3-диоксазепан : пропаргиловый эфир : CuCl = 1:2:(0.03-0.07) в атмосфере аргона при температуре 80°С и атмосферном давлении в среде толуола в течение 5-7 ч. 1 табл., 10 пр.

Способ получения полиядерных тетрааминов, содержащих мостиковые атомы

Изобретение относится к способу получения полиядерных тетрааминов, содержащих мостиковые атомы, указанной ниже общей формулы, где R=H, Ar=(I); R=H, Ar=(II); R=H, Ar=(III); R=CF, Ar=(IV), которые могут найти применение в качестве мономеров для синтеза различных полигетероариленов - полифенилхиноксалинов, полинафтоиленбензимидазолов и полибензимидазолов. Способ включает процессы взаимодействия бисфенолов с 5-хлор-4-R-2-нитроанилином при микроволновой активации и восстановления полиядерных динитродиаминов в условиях гетерогенного катализа. При этом ароматическое нуклеофильное замещение атома хлора проводят в 1-бутил-3-метилимидазолий тетрафторборате в присутствии ацетата калия при мощности микроволнового излучения 160 Вт и температуре 100°С в течение 2 мин при молярном соотношении 5-хлор-4-R-2-нитроанилин:бисфенол=1:0.5. Процесс восстановления проводят в изопропиловом спирте при 60°С, давлении 20 бар в присутствии катализатора 10% Pd/C в течение 30 мин. Предлагаемый способ позволяет уменьшить ...

МИНИМИЗАЦИЯ ЛЕТУЧИХ СЕРАОРГАНИЧЕСКИХ ПОБОЧНЫХ ПРОДУКТОВ ПРИ КВАТЕРНИЗАЦИИ АМИРОВ ДИМЕТИЛСУЛЬФАТОМ, ВЫПОЛНЯЕМОЙ В ПРИСУТСТВИИ ГИПОФОСФОРИСТОЙ КИСЛОТЫ

... 1. Способ минимизации запаха при кватернизации аминов диметилсульфатом, выполненной в присутствии гипофосфористой кислоты, который включает проведение указанной кватернизации в присутствии диметилсульфата, где указанный диметилсульфат содержит сернистый ангидрид в количестве меньшем, чем 20 ч./млн. 2. Способ по п.1, где указанный запах вызывают летучие сераорганические побочные продукты. 3. Способ по п.2, в котором указанный диметилсульфат содержит меньше, чем 8 ч./млн, сернистого ангидрида. 4. Способ по п.3, в котором указанный диметилсульфат содержит меньше, чем 5 ч./млн, сернистого ангидрида. 5. Способ получения сложноэфирной четвертичной аммониевой соли, имеющей улучшенный профиль запаха, который включает этерификацию алканоламина жирной кислотой, в присутствии катализатора этерификации/восстановительного отбеливающего агента, имеющего стандартный восстановительный потенциал, составляющий, по крайней мере, 0,5 В, для получения аминозамещенного сложного эфира, и последующую кватернизацию ...

ПРОЦЕСС ПОЛУЧЕНИЯ СОЕДИНЕНИЙ-ПРЕДШЕСТВЕННИКОВ ДЛЯ РАДИОАКТИВНЫХ ГАЛОГЕНПОМЕЧЕННЫХ СОЕДИНЕНИЙ

... 1. Способ получения соединения-предшественнника радиоактивного соединения, помеченного фтором, который включает ! стадию взаимодействия, обеспечивающего условия для взаимодействия раствора, содержащего вещество со следующей химической формулой (1) ! ! где R1 обозначает защитную группу карбоксильной группы, а R2 - защитную группу аминогруппы вместе с основанием и соединением, реагирующим с OH-группой соединения с химической формулой (1), при этом защитная группа становится уходящей группой, ! а также ! стадию очистки реакционного раствора, получаемого на стадии взаимодействия, для получения практически индивидуального стереоизомера вещества со следующей химической формулой (2) ! ! где R1 обозначает защитную группу карбоксильной группы, R2 - защитную группу аминогруппы, а R3 - уходящую группу. ! 2. Способ получения по п.1, в котором соединение, реагирующее с OH-группой соединения с химической формулой (1), становящееся уходящей группой на стадии взаимодействия, представляет собой одно или ...

ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ НА ОСНОВЕ ГЕНОТИПА ИЛИ ФЕНОТИПА

... 1. Фармацевтическая композиция комбинированного препарата с фиксированными дозами, содержащая исходное вещество, действие которого зависит от количества или активности экспрессируемых вариантов белков, вариантов ферментов, вариантов рецепторов или вариантов транспортеров, и по меньшей мере его метаболит.2. Композиция по п. 1, доза которой определяется в зависимости от генотипа или фенотипа.3. Композиция по п. 1 и 2, отличающаяся тем, что включает тамоксифен и эндоксифен.4. Композиция по п. 3, отличающаяся тем, что включает 15-25 мг тамоксифена и 0,25-5,0 мг эндоксифена.5. Композиция по п. 4 для пациентов с CYP2D6 IM, включающая 15-25 мг тамоксифена и 0,25-2,00 мг эндоксифена.6. Композиция по п. 4 для пациентов с CYP2D6 РМ, включающая 15-25 мг тамоксифена и 1,0-5,0 мг эндоксифена.7. Способ получения фармацевтической композиции комбинированного препарата с фиксированными дозами по любому из пп. 1-4, включающий следующие этапы:а) ввод организма, его генотипа или фенотипа, исходного вещества ...

АНАЛОГИ ХОЛИНА В КАЧЕСТВЕ РАДИОАКТИВНОГО ИНДИКАТОРА

... 1. Соединение формулы (I):где:каждый из R, R, Rи Rнезависимо представляет собой водород или дейтерий (D);каждый из R, Rи Rнезависимо представляет собой водород, R, -(CH)R, -(CD)R, -(CF)R, -CH(R)или -CD(R);Rпредставляет собой независимо водород, -OH, -CH, -CF, -CHOH, -CHF, -CHCl, -CHBr, -CHI, -CD, -CDOH, -CDF, CDCl, CDBr, CDI или -CH;m означает целое число от 1 до 4;каждый из X и Y независимо представляет собой водород, дейтерий (D) или F;Z представляет собой галоген, выбранный из F, Cl, Br и I, или радиоактивный изотоп; иQ означает анионный противоион;при условии, что указанное соединение формулы (I) не является фторметилхолином, фторметил-этил-холином, фторметил-пропил-холином, фторметил-бутил-холином, фторметил-пентил-холином, фторметил-изопропил-холином, фторметил-изобутил-холином, фторметил-втор-бутил-холином, фторметил-диэтил-холином, фторметил-диэтанол-холином, фторметил-бензил-холином, фторметил-триэтанол-холином, 1,1-дидейтерофторметилхолином, 1,1-дидейтерофторметил-этил-холином ...

УМЯГЧИТЕЛЬ ДЛЯ ТКАНИ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

... 1. Способ получения умягчителя для ткани, содержащего эфиркват формулы 1:[Формула 1]в которой А и В каждый независимо представляет собой CHCHOH или CHCHOCR, иRи Rкаждый независимо выбран из группы, состоящей из линейной или разветвленной алкил-группы и алкенил-группы С-Си комбинации их групп,который содержит осуществление первой реакции переэтерификации жирную кислоту содержащего масла и третичного гидроксиламина при температуре 110-130°C в условиях давления 50 мм рт.ст. (6,5 кПа) или менее и осуществление второй реакции переэтерификации при температуре 130-160°C, которая увеличивается в тот момент, когда 40-60% масла превращается в реагент для получения сложного эфира гидроксиламина и жирной кислоты; иосуществление реакции кватернизации при взаимодействии полученного таким образом сложного эфира гидроксиламина и жирной кислоты с кватернизующим агентом в растворителе с получением эфирквата формулы 1, указанной выше.2. Способ получения по п.1, в котором реактором является замкнутый реактор ...

ПРИМЕНЕНИЕ СОЕДИНЕНИЙ АЗОТА, КВАТЕРНИЗИРОВАННЫХ АЛКИЛЕНОКСИДОМ И ЗАМЕЩЕННОЙ ГИДРОКАРБИЛОМ ПОЛИКАРБОНОВОЙ КИСЛОТЫ, В КАЧЕСТВЕ ПРИСАДОК К ТОПЛИВАМ И СМАЗОЧНЫМ МАТЕРИАЛАМ

СПОСОБ ПОЛУЧЕНИЯ N-АЛКИЛ(ФЕНИЛ)-N,N-БИС[4-АЛКОКСИ(ФЕНОКСИ-, БЕНЗИЛОКСИ-, ПРОП-2-ИНИЛОКСИ)-2-БУТИНИЛ]АМИНОВ

СПОСОБ ПОЛУЧЕНИЯ (1R,2R)-3-(3-ДИМЕТИЛАМИНО-1-ЭТИЛ-2-МЕТИЛ-ПРОПИЛ)-ФЕНОЛА

... 1. Способ получения (1R,2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенола или его соли присоединения кислоты, который включает стадию ! (а) взаимодействие соединения общей формулы (I), ! ! где R представляет собой -C1-6-алкил, -C3-8-циклоалкил, -C1-3-алкилен-фенил, -C1-3-алкилен-нафтил, тетрагидропиранил или -C(=O)-C1-6-алкил, ! с этилмагний галогенидом в инертной реакционной среде в условиях Гриньяра, ! (б) перенос таким образом полученного соединения общей формулы (II), ! ! где R имеет значение, указанное выше, ! на соединение общей формулы (III), ! ! где R имеет значение, указанное выше, ! необязательно в форме соли присоединения кислоты, ! (в) снятие защиты с полученного таким образом соединения общей формулы (III) с образованием (1R,2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенола формулы (IV), ! ! (г) необязательно превращение таким образом полученного (1R, 2R)-3-(3-диметиламино-1-этил-2-метил-пропил)-фенола в соль присоединения кислоты. ! 2. Способ по п.1, отличающийся тем, ...

СПОСОБ ПОЛУЧЕНИЯ НЕНАСЫЩЕННОЙ ЧЕТВЕРТИЧНОЙ АММОНИЕВОЙ СОЛИ

... 1. Способ получения ненасыщенной четвертичной аммониевой соли, включающий:взаимодействие метилхлорида в первом сосуде со стехиометрическим избытком ненасыщенного третичного амина в присутствии воды для формирования реакционной смеси, содержащей ненасыщенную четвертичную аммониевую соль и остаточный ненасыщенный третичный амин;передачу части реакционной смеси во второй сосуд;разделение фаз в части реакционной смеси во втором сосуде для получения первой фракции, содержащей ненасыщенную четвертичную аммониевую соль и воду, и второй фракции, содержащей остаточный ненасыщенный третичный амин;удаление части первой фракции из второго сосуда для извлечения четвертичной аммониевой соли в качестве продукта; ивозвращение в цикл части второй фракции из второго сосуда в первый сосуд для использования в указанном взаимодействии метилхлорида со стехиометрическим избытком ненасыщенного третичного амина;причем ненасыщенный третичный амин представлен формулой:где Rявляется водородом или метилом; иненасыщенная ...

СПОСОБ ПОЛУЧЕНИЯ СОЕДИНЕНИЙ 2-АМИНО-1,3-ПРОПАНДИОЛА И ИХ СОЛЕЙ

УСОВЕРШЕНСТВОВАННЫЕ СПОСОБЫ ОРТО-АЛКИЛИРОВАНИЯ

... 1. Способ получения соединения формулы I где A представляет собой O или N-L; каждый L независимо представляет собой H или ацильную группу; K, вместе с двумя смежными связанными с ним атомами углерода, представляет собой фенильное кольцо, 5- или 6-членное гетероароматическое кольцо или ароматическую 8-, 9- или 10-членную конденсированную карбобициклическую или гетеробициклическую кольцевую систему, где каждое кольцо или кольцевая система является необязательно замещенным(-ой); R1 представляет собой H, C1-C4 -алкил или CO2R3; R2 представляет собой H или C1-C4-алкил; и R3 представляет собой C1-C4-алкил; включающий гидрирование соединения формулы II где n равно 0, 1 или 2; R4 представляет собой CHR1R2; и A, K, L, R1, R2 и R3 определены как указано для формулы I, в присутствии катализатора, включающего палладий, с образованием соединения формулы I. 2. Способ по п.1, в котором n равно 0. 3. Способ по п.1, в котором A представляет собой N-L в формуле I и, кроме того, включающий перед стадией гидрирования ...

Способ получения кислотно-аддитивных солей 3,4-диизобутирилокси- @ -метилфенэтиламина

Изобретение касается замещенных арилалифатических аминов, в частности кислотно-аддитивных солей 3,4-ди- изобутирилокси-Н-метилфенэтиламина (ФЭА), которые используют в медицине. Для упрощения процесса и повьппения выхода ФЭА в способе используют другие исходные соединения, которые пе- рерабатьшают в целевой ФЭА другим путем . Синтез ФЭА ведут гидрогенизацией ,3,4-диметокси-фенэтиламина, бенз- и формальдегида в присутствии катализатора Pd/C. Полученный гидробромид К-бензил-Н-метил-З,4-диметоксифен- этиламина превращают в соответствующие диоксисоединения с помощью НВг с последующей обработкой изобутирил- хлоридом в присутствии основания. Далее продукт гидрогенизируют в присутствии Pd/C. Полученный продукт либо вьщеляют, либо превращают в другую кислотно-аддитивную соль. Выход гидрохлорида ФЭА 90%,т.пл. 154,5- 157,. Использование доступных исходных (вместо этинина) упрощает процесс. i (У) с а ...

Способ получения -( -хлорэтил)-динитротрифторметиланилинов

Способ получения 82-93 мас.% водной суспензии хлорида 2- (N,N,N - триметиламмонио) этилметакрилата

Изобретение относится к четвертичным аммониевым солям ,в частности, к получения водной суспензии хлорида 2-(N,N,N-триметиламмонио)этилметакрилата, применяемого в производстве синтетических полимеров. Цель - повышение качества целевого продукта. Синтез ведут реакцией 78-91%-ного водного раствора 2-(N,N-диметиламино)этилметакрилата с CH3CL при повышение температуры процесса с 35 до 70°С с предотвращением образования кристаллов. Затем полученный раствор охлаждают непосредственно или после смешения с раствором целевого продукта, предварительно охлажденного до 25°С, путем нанесения в виде тонкой пленки на охлажденную стеклянную или хромированную поверхность. Полученный продукт представляет собой в отличие от известного светло-желтую, полупрозрачную и полностью однородную массу, которая способна к распылению. 1 табл.

Verfahren zur Herstellung von Nadolol.

VERFAHREN ZUR HERSTELLUNG VON FESTEN ESTERQUATS

Verfahren zur Herstellung von ungesättigten Aminen

Verfahren zur Herstellung von 2-Aminomalonsäurederivaten

Isomerizing water-soluble salts of trans-tramadol, useful for preparing the cis-isomer, a known analgesic, comprises treatment with warm water in presence of acid catalyst

Method for isomerizing water-soluble salts of (RS, SR)-tramadol (I; 2-(dimethylaminomethyl) 1-(3-methoxyphenyl)cyclohexanol) into a salt of the desired (RR, SS)-(I) free base, is carried out in warm, aqueous solution and catalyzed by acid, with water being used as the nucleophilic reactant. ACTIVITY : Analgesic. No biological data given. MECHANISM OF ACTION : None given.

Verfahren zur Herstellung von Dimethyl-(3-aryl-buthyl)-aminverbindungen als pharmazeutische Wirkstoffe

Die vorliegende Erfindung betrifft ein Verfahren zur Dehydratisierung substituierter 4-Dimethylamino-2-aryl-butan-2-ol-Verbindungen sowie Verfahren zur Herstellung substituierter Dimethyl-(3-aryl-butyl)-amin-Verbindungen mittels heterogener Katalyse.

Compositions and methods

Primary, secondary and tertiary ammonium salts as ionic liquids

The invention provides ionic liquids and processes for their preparation. The liquids may either comprise a cation of the formula (I): N<+>HR<1>R<2>R<3>```(I) wherein R' is an optionally substituted group -R<4>-O-R<5>; R<2> and R<3> are each independently either hydrogen or optionally substituted hydrocarbyl, or R<2> and R<3> may be joined together with the N to form a heterocyclic group; R<4> is a divalent hydrocarbyl radical; and R<5> is hydrocarbyl; or a cation of the formula (II): N<+>HR<6>R<7>R<8>```(II) wherein R<6> is an optionally substituted alkanolyl group; R<7> is a hydrocarbyl group; and R<8> is either hydrogen or optionally substituted hydrocarbyl, or R<7> and R<8> may be joined together with the N to form a heterocyclic group. In each instance hydrocarbyl should be understood as any group containing carbon and hydrogen, which may also contain one or more heteroatoms. Preferred anions include halides, halogenated inorganic or organic anions, nitrates, ...

Use of ionic liquids

Methods of using ionic liquids comprising: providing an ionic liquid in first chemical form; using the ionic liquid for a first predetermined purpose; chemically modifying the ionic liquid to change it to a second chemical form; and using this second form of a second predetermined purpose. Particular forms of chemical modification include: protection or deprotection of ionic liquid cations, e.g. silylation, in order to alter the viscosity or melting point of the ionic liquid to induce phase changes or enable trapping/release of a solute from a solid matrix; ion exchange to alter viscosity (for use in hydraulic fluids or lubricants), refractive index (for use in optoelectronic systems), to induce a phase change (to partition a solute between two liquid phases) or to alter solubilising power (for selective precipitation of compounds e.g. penicillin); and changing counterion in order to modulate enzyme activity (e.g morphine dehydrogenase (MDH)). Preferred ionic liquid cations include 3-hydroxypropyl ...

Process for the manufacture of basically substituted phenol ethers

In the manufacture of basically substituted phenolic ethers by reacting an alkali salt of a mono- or poly-hydric phenol with a water-soluble salt of a tertiary alkylaminoalkyl halide, the reaction is effected under alkaline conditions in the presence of water as a solvent and at a temperature not above 60 DEG C. In Example 1, o-benzylphenol in an aqueous solution of caustic soda is treated at 50-60 DEG C. with an aqueous solution of b -diethylaminoethyl chloride hydrochloride to yield b -diethylaminoethyl-2-benzylphenol ether. Other examples describe the manufacture in similar fashion of b -dimethyl-aminoethyl-2-benzylphenol ether, b -diethylamino ethyl phenol ether, b -diethylaminoethyl-p-cresol ether, b -diethylaminoethyl-p-nitrophenol ether and 1, 2, 3-tris-(b -diethylaminoethoxy)-benzene (from pyrogallol and b -diethylaminoethyl chloride). The hydrochlorides of the products of the first five examples and the tris-ethoiodide of the product of the last example are described. Specifications ...

Novel compounds, methods for their manufacture, and uses thereof

Synthetic cannabinoid analogue compounds of formula (I), wherein X is a group as defined herein. Also provided is a pharmaceutical composition of compounds of formula (I). Also provided is a compound of formula (I), or pharmaceutical composition, for use in a method of treatment, or for use as a medicament; which may be for use in the treatment of, or for use as a medicament for treating, epilepsy, generalised seizure, tonic-clonic seizure. Also provided is a method of preparing a compound of formula (I), comprising reacting a compound of formula (II) with a compound of formula (III), both defined herein. The method may use a palladium catalyst. Also provided is a method of preparing compounds of formula (I), comprising reacting a compound of formula (II) with bis(pinacolato)diboron (B2pin2), and reacting the product of that with a compound of formula (IV). The steps of the method may use a palladium catalyst. Also provided is an intermediate compound of formula (II), for use in the preparation ...

Process for making N-ARYL-ANTHRANILIC acids and their derivatives.

The present invention relates to a process for the preparation of N-arylanthranilic acids, and a process for the preparation of N-aryl anthranilic esters, amides, and hydroxamic esters.

Fabric softener active composition

Fabric softener active composition

New derivatives of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol.

Fabric softener active composition

Fabric softener active composition

Process for making n-aryl-antranilic acids and their derivatives

Process for making n-aryl-antranilic acids and their derivatives

NEW PROCEDURE FOR THE PRODUCTION OF QUATERNÄRER ACID AND AMMONIUM SALTS

PROCEDURE FOR THE SELECTIVE REDUCTION OF AROMATIC CONNECTIONS

INDEN OF DERIVATIVES AS PHARMACEUTICALS

PROCEDURE FOR DEHYDRATISIERUNG the SUBSTITUTING 4DIMETHYLAMINO-2-ARYL-BUTAN-2-OL-VERBINDUNGEN AND PROCEDURE FOR the PRODUCTION of SUBSTITUTED DIMETHYL (3-ARYL-BUTYL) - AMINE CONNECTIONS of MEANS of HETEROGENEOUS CATALYSIS

SALTS OF POTASSIUM ATP CHANNEL OPENERS AND YOUR USES

PROCEDURE FOR THE PRODUCTION OF TOLTERODIN

RETROVIRALE PROTEASE INHIBITORS

PROCEDURE FOR THE PRODUCTION OF TRANS-1,1,2TRIPHENYL - BUT-1-EN DERIVATIVES.

PRODUCTION OF WITH ENANTIOMER ENRICHMENT ORTHO SUBSTITUTING ALPHA, ALPHA DIAROMATI METHANOLS

PROCEDURE FOR THE PRODUCTION OF HYDROCHLORIDES.

PROCEDURE FOR THE PRODUCTION OF DIARYLAETHERN.

PROCEDURE FOR the TRANSFORMATION OF 1,2-DIPHENYL-1 (4 (2-DIMETHYLAMINO-ETHOXY) - PHEN L>-1-BUTEN-E-ISOMEREN FOR TAMOXIFEN HYDROCHLORIDE.

DYNAMIC SEPARATION FROM ISOMERS AND SEPARATE ISOMERS

PROCEDURE FOR THE PRODUCTION OF OPTICALLY ACTIVE ONE AMINOALKOHOLEN THROUGH RACEMATSPALTUNG

RETROVIRUSPROTEASE INHIBITORS

PROCEDURE FOR the PRODUCTION OF N, n DIALKYLAMINOPHENYLALKANOLEN

PROCEDURE FOR THE PRODUCTION OF ESTERQUATS

ENANTIOSELEKTIVE ADDITION REACTION WITH THE HELP OF A ORGANOZINK OF REAGENT

SYNTHESIS OF OPTICALLY ACTIVE ONE AMINOINDANOL

PROCEDURE FOR the PRODUCTION THAT ENANTIOMEREN OF o DEMETHYLTRAMADOL

Amine salts of carboxylic acid herbicides

The invention generally involves combining specialty amines with herbicidal carboxylic acids to form a new generation of salts with improved characteristics. The salts contain a cation of an amine and an anion of a carboxylic acid herbicide. The amine is advantageously selected from mono-isobutylamine (MIBA), N-methylaminoethanol (MMEA), dimethylaminopropylamine (DMAPA), 2-dimethylaminoethanol (DMAE), methyldiethanolamine (MDEA), and 1,2-diaminopropane (1,2-DAP). The amine-herbicide combinations may possess one or more improved characteristics, including maximum loading, wettability, drift, viscosity, and volatilization.

A PROCESS FOR THE ENANTIOSPECIFIC SYNTHESIS OF INTERMEDIATES FOR HEXAHYDRO-BENZO(D)NAPHTHO(2,1-B)AZEPINES

Enzyme-catalyzed racemic cleavage of primary amines

Mono-nitration of aromatic compounds

Short synthesis of tolterodine, intermediates and metabolites

A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)- 1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

Alkylated heterocyclic reaction products useful as antioxidants

Intermediate compounds and processes for the preparation of tapentadol and related compounds

The present invention discloses processes for the preparation of 3-[(1,2)-3-(dimethyl- amino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), salts thereof and related compounds of formula (A), including stereoisomers and pharmaceutically acceptable salts thereof, and to certain intermediates used in such process.

CATALYTIC PROCESSES FOR THE PREPARATION OF N,N,N- TRISUBSTITUTED NITROGEN-CONTAINING COMPOUNDS

Method for the production of adrenaline

TRANSITION-METAL-CATALYZED CARBON-NITROGEN BOND-FORMING METHODS USING CARBENE LIGANDS

Organic ammonium salts of anionic pesticides

The invention relates to an organic ammonium salt of formula (I), wherein the symbols have the following meanings: A ...

Indene derivatives as pharmaceutical agents

Method for industrially preparing nitrogen substituted amino-5,6,7,8-tetrahydronaphthol

A method for industrially preparing a nitrogen substituted 6-amino-5,6,7,8-tetrahydronaphthol is disclosed. The method comprises reacting a nitrogen substituted amino-5,6,7,8-tetrahydronaphthol compound of formula (II) with a 2-substituted ethyl sulfonate compound of formula (III) under an alkaline condition and in the presence of a sulfite.

Aramchol salts

The present invention relates to salts of arachidyl amido cholanoic acid (Aramchol), pharmaceutical compositions comprising Aramchol salts, methods for their preparation, and methods of use thereof in medical treatment.

Method for the production of E-1-(4'-(2-dimethylaminoethoxy)-phenyl)-1-(3'-hydroxyphenyl) -2-phenyl-1-butene

New derivatives of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol

Efficient enantioselective addition reaction using an organozinc reagent

CHEMICAL PROCESSES AND PRODUCTS

Method for preparing 5-substituted oxazoles

LIGANDS FOR METALS AND METAL-CATALYZED PROCESSES

One aspect of the present invention relates to novel ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon- heteroatom and carbon-carbon bond-forming reactions. The subject processes provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.

PROCESS FOR THE PREPARATION OF AMINOALCOHOL DERIVATIVES AND THEIR FURTHER CONVERSION TO (1S,4R)- OR (1R,4S)-1-AMINO-4-(HYDROXYMETHYL)-2-CYCLOPENTENE

PROCESS FOR PREPARING ALKYLALKANOLAMINES

La présente invention concerne un procédé de préparation d'alkylalcanolamines, comprenant la réaction d'un composé carbonylé avec une hydroxyalkylamine, en présence d'hydrogène et d'un catalyseur.

PROCESSES FOR THE PREPARATION OF SQUARAINE COMPOSITIONS

Disclosed is an improved process for the preparation of squaraine compositions which comprises reacting squaric acid, an aromatic amine, and a composition selected from the group consisting of phenols and phenol squaraines, in the presence of an aliphatic alcohol, and an optional azeotropic substance.

PROCESS FOR PREPARATION OF N-(B-UCHLORO-ETHYL)-DINITRO-TRIFLUO ROMETHYL-ANILINES

SUBSTITUTED 2-AMINOMETHYLPHENOLS

PROCESS FOR THE PREPARATION OF SERINOL

A process of forming 2-amino-1,3-propanediol by reducing the compound, 5-nitro-1,3-dioxane and subsequently hydrolyzing the reduced compound.

PROCESS FOR THE PREPARATION OF 3,4-DI-ISOBUTYRYLOXY-N- METHYL-PHENETHYLAMINE

PROCESS FOR PREPARING 2-(4'-HYDROXYARYL)-2- (4'-AMINOARYL)-PROPANES

REDOX FLOW BATTERY ELECTROLYTES

The present invention relates to novel combinations of redox active compounds for use as redox flow battery electrolytes. The invention further provides kits comprising these combinations, redox flow batteries, and method using the combinations, kits and redox flow batteries of the invention.

DEZOCINE DERIVATIVE AND MEDICAL USE THEREOF

Provided are a dezocine derivative of formula I or a tautomer, optical isomer, oxynitride, solvate, pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutical composition comprising the same, a preparation method therefor, and a medical use thereof, the structure of the formula I is as follows: ...

PROCESSES AND COMPOUNDS

Useful processes of preparation and intermediates useful for the preparation of Compound 1, a selective estrogen receptor alpha (ERa) modulator/degrader (SERM/SERD), having utility for the treatment of ER+ cancers including breast cancer are described.

PROCESS FOR PREPARING ETHYLENEAMINE COMPOUNDS

The invention relates to a process for manufacturing polyethyleneannine compounds selected from the group of polyethyleneamines and hydroxyethylethyleneamines comprising the steps of - in an adduction step providing a CO2 adduct of a starting compound comprising a - NH-CH2-CH2-NH- moiety or a -NH-CH2-CH2-OH moiety, or HO-CH2-CH2-OH, - in a reaction step reacting a hydroxy-functional compound selected from the group of ethanolamines and dihydroxyethane with an amine-functional compound, wherein at least part of the total of hydroxy-functional compounds and amine-functional compounds is provided in the form of a CO2 adduct, to form CO2 adduct of a product polyethyleneannine compound, - in an elimination step converting CO2 adduct of product polyethyleneannine compound to the corresponding product polyethylene amine compound, wherein a fraction comprising a recycle compound comprising a -NH-CH2-CH2-NH- moiety or a -NH-CH2-CH2-OH moiety, or HO-CH2-CH2-OH, or CO2 adducts thereof, is provided ...

METHODS OF PREPARING HALIDE ANION FREE QUATERNARY AMMONIUM SALT MONOMERS, POLYMERIZATION METHODS THEREFOR, AND METHODS OF USE OF THE RESULTING POLYMERS

COMPOSITION FOR TREATING CANCER CONTAINING N,N-DIMETHYLPHYTOSPHINGOSINE

A composition and a kit for treating cancer comprising N, N- dimethylphytosphingosine. The composition represses the activity of sphingosine kinase, and therefore, intercepts various mechanisms which sphingosine kinase induces. For example, the composition blocks the phosphorylation of ceramide and sphingosine, thereby maintaining high concentration of ceramide and sphingosine. The ceramide and sphingosine induce apoptosis in cancer cells. Therefore, the composition according to the present invention induces apoptosis in cancer cells and accordingly kills the cancer cells.

PROCESS FOR THE PREPARATION OF CARNITINE CHLORIDE

HETEROBIFUNCTIONAL POLY(ETHYLENE GLYCOL) AND USES THEREOF

... ²²²The present invention provides bifunctional polymers, methods of preparing the ²same, and intermediates thereto. These compounds are useful in a variety of ²applications including the PEGylation of biologically active molecules. The ²invention also provides methods of using said compounds and compositions ²thereof.² ...

PROCESS FOR PREPARING DIHYDROXYTRIALKYLAMMONIUM HALIDES AND PRODUCTS THEREOF

MONO-NITRATION OF AROMATIC COMPOUNDS BY ADDITION OF SOLUTIONS OR SUSPENSIONS OF NITRATE SALTS TO ACIDS

A method of nitrating a compound selected from the group consisting of Formulas (AA) (BB) (CC) (DD) wherein Ar is a nitratable aromatic ring, R1, R2, R3, and R4 are hydrogen, alkyl or an aromatic groups, G is selected from the group consisting of CR1R2, O, S, SO and SO2, R is a heterocyclic ring or other groups bearing a basic nitrogen atom 10 and n is an an integer of 1 to 12 is provided.

Process for reduction of alpha-acyloxy sulfide derivatives

The present invention provides an efficient and scalable process to prepare the compound of formula 4 by reduction of the corresponding α-acyloxy sulfides.

Intermediate compounds and processes for the preparation of tapentadol and related compounds

The present invention discloses processes for the preparation of 3-[(1R,2R)-3-(dimethyl-amino)-1-ethyl-2-methyl-propyl]phenol (Tapentadol), salts thereof and related compounds of formula (A), including stereoisomers and pharmaceutically acceptable salts thereof, and to certain intermediates used in such process.

Novel Process for the Preparation of Nitrogen Substituted Aminotetralins Derivatives

The present invention provides an alternative synthesis of N-substituted aminotetralines comprising resolution of N-substituted aminotetralins of formula (II), wherein R 1 , R 2 and R 3 are as defined for compound of formula (I).

Methods for preparing ritodrine hydrochloride

Methods for preparing Ritodrine hydrochloride are provided. Also provided is non-hygroscopic, crystalline, polymorphic Ritodrine hydrochloride of Form I.

Novel method of preparing secondary amine compound using microflow reactor

Disclosed is a novel method of preparing a secondary amine compound using a microflow reactor. According to the method, a primary amine compound and a halide compound are allowed to react with each other in the microflow reactor, such that the production of a tertiary amine compound or an ammonium salt is minimized, whereby the secondary amine compound is efficiently prepared.

PROCESS FOR THE SYNTHESIS OF CHOLINE SALTS

A method to synthesize choline salts to be used as inexpensive ingredients for application in ionic liquids or other applications is disclosed. 1. A process for the synthesis of one or more choline salts , comprising:(a) providing an aqueous solution of choline;(b) combining the aqueous solution of choline with a hydrophobic organic solvent and an excess of free acid to form a first acidic, solution;(c) combining the first acidic solution with one or more alcohols to form a first extraction mixture;(d) separating the first extraction mixture into a lower phase, a middle phase and an upper phase; and(e) recovering the lower phase of the first extraction mixture to provide a first aqueous solution of a choline salt.2. A process according to further comprising:(f) combining the first aqueous solution of choline salt with an excess of free acid and a hydrophobic organic solvent to form a second acidic solution;(g) combining the second acidic solution with at least one alcohol and to form a second extraction mixture;(h) separating the second extraction mixture into a lower phase, a middle phase and an upper phase; and(i) recovering the lower phase of the second extraction mixture to provide a second aqueous solution of a choline salt.3. A process according to further comprising isolating the choline salt from the first aqueous solution of choline salt.4. A process according to further comprising isolating the choline salt from the second. aqueous solution of choline salt.5. A process according to further comprising recycling the hydrophobic organic solvent for further use in the process.4. A process according to wherein the alcohol comprises at least one Cto Calcohol.5. A process according to wherein the alcohol comprises ethanol claim 1 , propanol or isopropanol.6. A process according to wherein the hydrophobic organic solvent comprises a high-boiling-point alkane.7. A process according to wherein the hydrophobic organic solvent comprises cyclohexane.8. A process ...

METHOD FOR PRODUCTION OF F-18 LABELED AMYLOID BETA LIGANDS

This invention relates to methods, which provide access to [F-18]fluoropegylated (aryl/heteroaryl vinyl)-phenyl methyl amine derivatives. 2. A method according to claim 1 , wherein PG is selected from the group consisting of:a) Boc,b) Trityl andc) 4-Methoxytrityl.3. A method according to claim 1 , wherein LG is selected from the group consisting of:a) Halogen andb) Sulfonyloxy,Wherein Halogen is chloro, bromo or iodo.4. A method according to claim 3 , wherein Sulfonyloxy is selected from the group consisting of:a) Methanesulfonyloxy,b) p-Toluenesulfonyloxy,c) (4-Nitrophenyl)sulfonyloxy,d) (4-Bromophenyl)sulfonyloxy.5. A method according to claim 1 , wherein n=3 and X═CH.6. A method according to claim 1 , wherein n=3 claim 1 , X═CH claim 1 , R=Boc claim 1 , and LG=Methanesulfonyloxy.7. A method according to claim 1 , wherein the radiofluorination reaction is carried out in a mixture of acetonitrile and co-solvents claim 1 , wherein the percentage of acetonitrile is at least 50%.8. A method according to claim 7 , wherein the radiofluorination reaction is carried out in a mixture of acetonitrile and co-solvents claim 7 , wherein the percentage of acetonitrile is at least 70%.9. A method according to claim 7 , wherein the radiofluorination reaction is carried out in a mixture of acetonitrile and co-solvents claim 7 , wherein the percentage of acetonitrile is at least 90%.10. A method according to claim 1 , wherein 1.5-75 μmol claim 1 , preferably 10-30 μmol and even more preferably 12-25 μmol of compound of Formula II are used in Step 1.11. A method according to claim 1 , wherein the method is performed as a fully automated process.12. A kit claim 1 , comprising a sealed vial comprising a predetermined quantity of a compound of formula II of and a sealed vial comprising acetonitrile or acetonitrile and a co-solvent.13. A method according to claim 1 , wherein Step 3 comprises a purification by HPLC.14. A method according to claim 13 , wherein the HPLC solvent used in ...

PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF

The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. 130-. (canceled)32. The process according to claim 31 , wherein the halide is bromide and the metal is zinc or magnesium.33. The process according to claim 31 , wherein the ethyl metal halide is ethylmagnesium bromide.34. The process according to claim 32 , wherein the ethyl metal halide is used in a quantity between 1 and 5 equivalents with respect to compound (VIII).35. The process according to claim 31 , wherein the alkylation is carried out at a temperature between 0° C. and the boiling temperature of the solvent.36. The process according to claim 35 , wherein the alkylation is carried out at a temperature between 10 and 30° C.38. The process according to claim 37 , wherein the chiral acid is selected from D(−) mandelic acid claim 37 , D(−) 2-chloromandelic acid claim 37 , D(−) tartaric acid claim 37 , and (2R claim 37 ,3R)-O claim 37 ,O′-dibenzoyl tartaric acid.39. The process according to claim 38 , wherein the chiral acid is D(−) mandelic acid.40. The process according to claim 37 , wherein the polar solvent of step a′) is selected from: water claim 37 , aliphatic ketones and/or aliphatic alcohols claim 37 , used ...

Short synthesis of tolterodine, intermediates and metabolites

A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

PROCESSES FOR THE PREPARATION OF FESOTERODINE

The invention relates to improved process for the preparation of fesoterodine and its pharmaceutically acceptable salt, specifically fesoterodine fumarate of formula (1). The invention relates to solid state forms of a novel salt of fesoterodine and process for the preparation thereof. The invention also relates to highly pure fesoterodine fumarate substantially free of impurity X at RRT 1.37. The invention also provides solid particles of pure fesoterodine fumarate wherein 90 volume-percent of the particles (D90) have a size of higher than 200 microns. 1. Fesoterodine 2-chloro-mandelate.2. The fesoterodine 2-chloro-mandelate as claimed in claim 1 , which is in a crystalline form or an amorphous form.3. The fesoterodine 2-chloro-mandelate as claimed in claim 1 , wherein 2-chloro-mandelic acid is racemic(±) 2-chloro-mandelic acid claim 1 , S-(+)-2-chloro-mandelic acid claim 1 , or R-(−)-2-chloro-mandelic acid.4. The festerodine 2-chloro mandelate as claimed in claim 3 , wherein the 2-chloro-mandelic acid is S-(+)-2-chloro-mandelic acid.5. Fesoterodine 2-chloro-mandelate as claimed in claim 1 , with one or more of the following properties:i) a powder X-ray diffraction pattern having peaks at about 9.9, 12.9, 14.2, 19.2, 20.7 and 24.9±0.2 degrees 2-theta;{'figref': {'@idref': 'DRAWINGS', 'FIG. 5'}, 'ii) a powder X-ray diffraction pattern as depicted in ;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 6'}, 'iii) a DSC thermogram having an endotherm peak at about 162° C. or substantially as depicted in ; or'}{'sup': '−1', 'figref': {'@idref': 'DRAWINGS', 'FIG. 7'}, 'iv) an infrared spectrum having absorption bands at about 3346, 2985, 2970, 2939, 2873, 2603, 2368, 1755, 1620, 1492, 1388, 1328, 1224, 1190, 1120, 1087, 1062, 1031, 970, 916, 867, 819, 759, 732, 705, 607, 582. 561, 522 and 501 cmor a spectrum depicted in .'}6. A process for the preparation of fesoterodine 2-chloro-mandelate claim 1 , the process comprising obtaining a solution of fesoterodine in one or more ...

METHODS FOR THE PREPARATION OF HIV ATTACHMENT INHIBITOR PIPERAZINE PRODRUG COMPOUND

A method for making the compound 2. The process of claim 1 , wherein Ris —SOAryl.3. The process of claim 2 , wherein Xis —H.4. The process of claim 3 , wherein Xis —H.6. The process of claim 5 , wherein Ris —SOAryl.7. The process of claim 6 , wherein Xis —H.8. The process of claim 7 , wherein Xis —H.10. The process of claim 9 , wherein Ris —SOAryl.11. The process of claim 10 , wherein Xis —H.12. The process of claim 11 , wherein Xis —H.14. The process of claim 13 , wherein R=tert-butyl claim 13 , Rand Xare —H.15. The process of claim 13 , wherein Ris —OMe.19. The process of claim 18 , wherein said first solvent is selected from the group of NMP claim 18 , DMSO claim 18 , MeCN claim 18 , MeOH claim 18 , acetone and a carboxylic acid.20. The process of claim 18 , wherein said second solvent is selected from the group of an alkyl ketone claim 18 , heptane claim 18 , toluene claim 18 , and ethyl acetate.21. The process of claim 18 , wherein the first solvent is acetic acid claim 18 , and said second solvent is acetone. This non-provisional application claims the benefit of U.S. Provisional Application Ser. No. 61/596,362 filed Feb. 8, 2012.The invention relates to methods of making HIV attachment inhibitor compounds useful as antivirals, and in particular, to methods of making the piperazine prodrug compound identified as 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-piperazine. The invention also relates to the compounds, including intermediates, obtained by the processes herein set forth.HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with tens of millions of people still infected worldwide at the end of 2011. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2005, for example, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the ...

SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

Provided are immediate or prolonged administration of certain salts of Kchannel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving Kchannels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals. 2. The method of wherein said cation source is an alkali metal hydroxide.3. The method of wherein said cation source is sodium hydroxide or potassium hydroxide.4. The method of wherein said solvent is selected from the group consisting of acetonitrile claim 3 , low molecular weight ketones claim 3 , and tetrahydrofuran.5. The method of wherein said cation source is an organic cation source comprising an ammonium or at least one tertiary amine group.6. The method of wherein said cation source is choline hydroxide or hexamethyl hexamethylene diammonium dihydroxide.7. The method of wherein said solvent is selected from the group consisting of acetonitrile claim 6 , low molecular weight ketones claim 6 , tetrahydrofuran claim 6 , and 2-methyl tetrahydrofuran.8. The method of wherein said cation source is choline hydroxide claim 6 , and said solvent is selected from the group consisting of acetonitrile claim 6 , low molecular weight ketones claim 6 , tetrahydrofuran claim 6 , and 2-methyl tetrahydrofuran.9. The method of wherein said compound of Formulae I-IV is dissolved in a solvent at a ratio of about 1 g compound of Formulae I-IV to about 1 to 5 mL solvent.10. The method of further comprising adding a co-solvent prior to the step of removing the solvent.11. The method of wherein said co-solvent is selected from the group consisting of methyl tert-butyl ether (MTBE) claim ...

CRYSTALLINE FORMS OF (R)-3-[N-(3'-CHLOROBIPHENYL-4-YLMETHYL)-N'-(3-HYDROXYISOXAZOLE-5-CARBONYL)HYDRAZINO]-2-HYDROXYPROPIONIC ACID ISOPROPYL ESTER

The invention provides crystalline forms of (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester. This invention also provides pharmaceutical compositions comprising the crystalline compound, processes and intermediates for preparing the crystalline compound, and methods of using the crystalline compound to treat diseases. 1. A crystalline (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester , selected from:a neutral monohydrate Form 1 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.26±0.20, 14.68±0.20, 15.64±0.20, 16.36±0.20, 18.52±0.20, 20.40±0.20, 21.08±0.20, 21.48±0.20, 21.68±0.20, 23.18±0.20, 24.50±0.20, 24.80±0.20, 25.34±0.20, and 26.56±0.20;a neutral Form 2 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.48±0.20, 8.02±0.20, 9.38±0.20, 12.24±0.20, 14.86±0.20, 18.72±0.20, 20.94±0.20, 21.34±0.20, 22.32±0.20, and 24.68±0.20;a neutral solvated Form 2′ characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.26±0.20, 8.05±0.20, 12.20±0.20, 14.48±0.20, 15.84±0.20, 16.22±0.20, 18.78±0.20, 20.60±0.20, 21.29±0.20, 21.74±0.20, 23.10±0.20, 24.16±0.20, and 24.44±0.20;a neutral anhydrous Form 3 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.12±0.20, 8.86±0.20, 11.92±0.20, 13.68±0.20, 16.10±0.20, 18.12±0.20, 18.46±0.20, 19.06±0.20, 19.48±0.20, 20.60±0.20, 21.28±0.20, 24.46±0.20, 25.94±0.20, and 26.40±0.20;a neutral anhydrous Form 4 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.70±0.20, 13.00±0.20, 16.00±0.20, 16.94±0.20, 17.36±0.20, 18.72±0.20, 19.00±0.20, 19.78±0.20, 20.24±0.20, 21.70±0.20, 23.68±0.20, and 27.94±0.20;a tromethamine salt characterized by a powder x-ray diffraction pattern ...

PHENOXYPROPANOL DERIVATIVES AND THEIR USE IN TREATING CARDIAC AND CARDIOVASCULAR DISEASES

A compound of formula I-0, and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: 2. The compound as claimed in wherein Ris selected from unsubstituted and substituted Ccycloalkyl claim 1 , Ccycloalkyl-Calkyl claim 1 , Calkyl claim 1 , Caryl-Calkyl claim 1 , Calkoxy-Caryl-Calkyl.3. The compound as claimed in wherein Xis selected from CO claim 1 , CS claim 1 , SOand a single bond.4. The compound as claimed in wherein Rand Rare selected from ROZO as hereinbefore defined claim 1 , m- claim 1 ,p-(OCH)or o- claim 1 , m- or p-OH claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , NH claim 1 , R claim 1 , OR claim 1 , or CFor a combination thereof.12. A process for the preparation of a compound of formula I-0 or subformulae as defined in .14. A composition comprising a therapeutically effective amount of a compound of formula I-0 or subformulae or its pharmaceutically acceptable salt and physiologically hydrolysable derivative as defined in in association with one or more pharmaceutical carriers or diluents.15. The use of a compound of formula I-0 or subformulae or pharmaceutically acceptable salt or composition as defined in in the prevention or treatment of a condition selected from ischaemic heart disease claim 1 , hypertension and heart failure claim 1 , more preferably with concomitant respiratory disease claim 1 , in particular asthma or COPD.16. A method of treating a condition selected from ischaemic heart disease (also known as myocardial infarction or angina) claim 1 , hypertension and heart failure claim 1 , restenosis and cardiomyopathy claim 1 , more preferably with concomitant respiratory disease claim 1 , in particular asthma or COPD claim 1 , said method comprising administering to a subject in need thereof claim 1 , a compound of formula I-0 or subformulae or pharmaceutically acceptable salt or composition thereof as defined in in an amount sufficient to treat the condition.17. A method of ...

Process to prepare treprostinil, the active ingredient in remodulin®

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.

BENZYLAMINE HYDROPHOBE

The present invention relates to a compound characterized by the following formula: 3. The compound of wherein Ris n-butyl or 2-ethylhexyl.7. The method of wherein Ris n-butyl or 2-ethylhexyl; m is 0; and p is 1. The present invention idea relates to an amine-based hydrophobe useful in preparing hydrophobically modified alkylene oxide urethane polymers, which are useful as rheology modifiers for coatings formulations.Rheology modifiers are typically designed to impart desirable rheological properties to coating formulations over a wide shear rate range. U.S. Pat. No. 7,741,402 discloses ethylene oxide urethane polymers modified with hydrophobes that contain organic bases such as secondary or tertiary amines (amine-modified HEURs), the presence of which provides for viscosity control through a pH trigger. When the pH of the HEUR composition is sufficiently low with respect to the pKof the incorporated base, the basic groups are protonated and the viscosity is relatively low; when the pH is sufficiently high, associative thickening occurs. Thus, incorporation of basic hydrophobes into the HEUR polymer allows relatively high concentration of polymer to be dissolved in water at low pH; once the solution is added to the high pH environment of paint coatings, the base is deprotonated and the associative thickening mechanism activated.Amine-modified HEURs can be sensitive to the pH of the paint formulation to which it is added. For example, the pH of the formulation, through time and heat aging, may decrease to a level below a critical pH conducive to associative thickening, thereby resulting in a poorer formulation; consequently, it would be desirable to discover a hydrophobe, more particularly an amine-based hydrophobe, that preserves the desired viscosity of the formulation in face of pH-lowering mechanisms.The present invention addresses a need by providing, in one aspect, a compound characterized by the following formula:where Ris C-C-alkyl, phenyl, naphthyl, C-C- ...

ORGANIC AMINE SALTS OF AZILSARTAN, PREPARATION METHOD AND USE THEREOF

Disclosed are organic amine salts of azilsartan, a preparation method and use thereof. In particular, disclosed are organic amine salts of azilsartan, their preparation method, the pharmaceutical composition comprising the compound in a therapeutically effective quantity, and their use for the manufacture of antihypertensive medicaments. 1. An organic amine salt of Azilsartan , wherein the ratio of Azilsartan to organic amine is m:1 and m is an integer selected from 2 to 10.2. The organic amine salt of Azilsartan according to claim 1 , wherein the ratio of Azilsartan to organic amine is 2:1.3. The organic amine salt of Azilsartan according to claim 1 , wherein the organic amine salt of Azilsartan exists in the form of a single molecule or a complex.4. The organic amine salt of Azilsartan according to claim 3 , wherein the organic amine is selected from the group consisting of methylamine claim 3 , dimethylamine claim 3 , trimethylamine claim 3 , ethylamine claim 3 , diethylamine claim 3 , triethylamine claim 3 , ethanolamine claim 3 , piperazidine claim 3 , dibenzylethylenediamine claim 3 , meglumine claim 3 , tromethamine claim 3 , tetramethyl quaternary ammonium claim 3 , tetraethyl quaternary ammonium and choline.7. A process for preparing the organic amine salt of Azilsartan according to claim 1 , comprising adding Azilsartan acid and an organic amine respectively into an alcoholic organic solvent at room temperature or under heating to obtain the salt.8. A process for preparing the organic amine salt of Azilsartan of formula (III) according to claim 6 , the process comprising adding Azilsartan acid and a choline alcohol solution into an alcoholic organic solvent.9. The process according to claim 7 , wherein the alcoholic organic solvent is selected from the group consisting of methanol claim 7 , ethanol claim 7 , propanol and isopropanol.10. A pharmaceutical composition for the treatment of hypertension claim 1 , comprising a therapeutically effective amount of ...

Process for preparing styrene derivatives

A process is provided which allows the synthesis of a large number of styrene derivatives with formation of C—C bonds, with use being possible of economically advantageous substrates, readily available carbon nucleophiles, and both inexpensive and environmentally unproblematic catalyst systems, permitting reaction under mild conditions and a high compatibility with functional groups on the reactants involved.

Process for the Synthesis of Aminobiphenylene

The present invention relates to a process for the synthesis of 2-aminobiphenylene and derivatives thereof by reacting a benzene diazonium salt with an aniline compound under basic reaction conditions. 127-. (canceled)31. The process of claim 28 , wherein the reaction is performed at a pH of 9.1 or greater32. The process of claim 28 , wherein the reaction is performed in the presence of at least one solvent.33. The process of claim 32 , wherein the solvent is an aqueous solvent.34. The process of claim 28 , wherein the reaction is performed in the presence of water and of at least one base.35. The process of claim 34 , wherein the base is selected from the group consisting of alkali metal hydroxides claim 34 , alkaline earth metal hydroxides claim 34 , alkali metal carbonates and alkali metal phosphates claim 34 , and is preferably sodium hydroxide or potassium hydroxide.36. The process of claim 28 , wherein the reaction is performed within the temperature range from 50 to 130° C.37. The process of claim 28 , wherein the compound of the formula 1 or the compound of the formula 2 or both compounds 1 and 2 are used in the reaction dispersed in an alkaline medium.38. The process of claim 37 , wherein the pH of the alkaline medium is at least 9.1.39. The process of claim 28 , wherein claim 28 , in a first step claim 28 , a compound of the formula 1 is reacted with a base in aqueous medium and claim 28 , in a second step claim 28 , the dispersion obtained is added to the compound of the formula 2.40. The process of claim 39 , wherein the pH of the dispersion obtained is at least 9.1.41. The process of claim 39 , wherein the compound 2 claim 39 , prior to addition of the dispersion claim 39 , is brought to a temperature of 50 to 130° C.42. The process of claim 28 , wherein the compound of the formula 2 is initially charged in an alkaline medium and the compound of the formula 1 is added.43. The process of claim 42 , wherein the compound of the formula 2 is initially ...

METHOD FOR PRODUCTION OF F-18 LABELED AMYLOID BETA LIGANDS

This invention relates to methods, which provide access to F-18 labeled stilbene derivatives. 2. A compound according to claim 1 ,Wherein PG is selected from the group consisting of:a) Boc,b) Trityl andc) 4-Methoxytrityl3. A compound according claim 1 ,whereinArylsulfonyloxy is selected from the group consisting ofp-Toluenesulfonyloxy, 4-Cyanophenylsulfonyloxy, 4-Bromophenylsulfonyloxy, 4-Nitrophenylsulfonyloxy, 2-Nitrophenylsulfonyloxy, 4-Isopropyl-phenylsulfonyloxy, 2,4,6-Triisopropyl-phenylsulfonyloxy, 2,4,6-Trimethylphenylsulfonyloxy, 4-tert-Butyl-phenylsulfonyloxy, 4-Adamantylphenylsulfonyloxy and 4-Methoxyphenylsulfonyloxy.7. A method according to claim 5 , wherein the method is a fully automated method.9. A kit according to claim 8 ,whereinPG is selected from the group comprising:a) Boc,b) Trityl andc) 4-Methoxytrityl10. A kit according to claim 8 ,WhereinArylsulfonyloxy is selected from the group comprising:a) p-Toluenesulfonyloxyb) (2-Nitrophenyl)sulfonyloxy,c) (4-Cyanophenyl)sulfonyloxyd) (4-Bromophenyl)sulfonyloxy,e) (4-Adamantylphenyl)sulfonyloxy.11. A kit comprising at least one sealed container containing a compound as defined by . This invention relates to compounds and methods, which provide access to F-18 labeled stilbene derivatives.4-[(E)-2-(4-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}phenyl)vinyl]-N-methylaniline has been labeled with [F-18]fluoride and is claimed by patent application WO2006066104 and members of the corresponding patent family.The usefulness of this radiotracer for the detection of Aβ plaques have been reported in the literature (W. Zhang et al., Nuclear Medicine and Biology 32 (2005) 799-809; C. Rowe et al., Lancet Neurology 7 (2008) 1-7).The synthesis of 4-[(E)-2-(4-{2-[2-(2-[F-18]fluoroethoxy)ethoxy]ethoxy}phenyl)-vinyl]-N-methylaniline has been described before:Very recently, further methods have been described:So far, one-pot radiolabelings have been performed using a mesylate precursor. It is know, that for F-18 labeling of ...

Method for Forming Allylic Alcohols

A method of performing a chemical reaction includes reacting an allyl donor and a substrate in a reaction mixture, and forming a homoallylic alcohol in the reaction mixture. The substrate may be an aldehyde or a hemiacetal. The reaction mixture includes a ruthenium catalyst, carbon monoxide at a level of at least 1 equivalent relative to the substrate, and water at a level of at least 1 equivalent relative to the substrate, and an amine at a level of from 0 to 0.5 equivalent relative to the substrate. The reaction mixture may also include a halide, and the equivalents of the amine may be similar to those of the halide. The reacting includes maintaining the reaction mixture at a temperature of at least 40° C. The method may be catalytic in metal, environmentally benign, amenable to large-scale applications, and applicable to a wide range of substrates. 1. A method of performing a chemical reaction , comprising:reacting an allyl donor and a substrate selected from the group consisting of an aldehyde and a hemiacetal in a reaction mixture, a ruthenium catalyst, a halide, carbon monoxide at a level of at least 1 equivalent relative to the substrate, water at a level of at least 1 equivalent relative to the substrate, and an amine at a level of from 0.01 to 0.5 equivalent relative to the substrate; or', 'a halide-free ruthenium catalyst, carbon monoxide at a level of at least 1 equivalent relative to the substrate, water at a level of at least 1 equivalent relative to the substrate, and an amine at a level of from 0 to 0.5 equivalent relative to the substrate, where the reaction mixture does not include a halide;, 'the reaction mixture comprising'}where the reacting comprises maintaining the reaction mixture at a temperature of at least 40° C.; andforming a homoallylic alcohol in the reaction mixture.2. The method of claim 1 , where the reaction mixture comprises a ruthenium catalyst claim 1 , a halide claim 1 , carbon monoxide at a level of at least 1 equivalent ...

BROMFENAC ORGANIC SALTS AND PREPARATION METHOD, COMPOSITION AND USE THEREOF

Provided are bromfenac organic salts and preparation method, composition and use thereof. The bromfenac organic salt has the structure as shown in the following Formula I, wherein A represents an organic base. Also provided are a method for the preparation of the bromfenac organic salt, a composition comprising the bromfenac organic salts, a use of the bromfenac organic salts or the composition thereof in manufacture of a medicament for treatment and/or prophylaxis of an inflammation or for analgesia, and a method for treatment and/or prophylaxis of an inflammation or for analgesia. 3. A method for preparing the bromfenac organic salt according to claim 1 , comprising the steps:1) dissolving bromfenac in an organic solvent, heating to dissolve, then adding an organic base in equimolar amount, stirring until the end of reaction;2) concentrating and evaporating the reaction solution to dry to obtain a light yellow or orange yellow solid; and3) recrystallizing the solid obtained in step 2) to obtain the bromfenac organic salt.4. The method according to claim 3 , wherein said organic solvent in step 1) is one or more selected from the group consisting of methanol claim 3 , ethanol claim 3 , acetone claim 3 , n-butanol and toluene; and said organic base is a nitrogen-containing organic base.5. The method according to claim 3 , wherein the temperature of heating in step 1) is 25-80° C.6. The method according to claim 3 , wherein the time for stirring and reacting in step 1) is 0.5-2 hours.7. The method according to claim 3 , wherein the recrystallization in step 3) is performed at 0° C. or below.8. The method according to claim 3 , further comprising step 4): vacuum drying the crystal obtained by recrystallizing.9. A composition claim 1 , comprising the bromfenac organic salt according to .10. (canceled)11. A method for treatment and/or prophylaxis of an inflammation or for analgesia claim 1 , comprising a step of administering an effective amount of the bromfenac organic ...

METHOD FOR PRODUCING N-SUBSTITUTED AMINE COMPOUNDS THROUGH CATALYZED ALKYLATION

The invention relates to a method for producing a N-substituted amine compound by catalyzed alkylation. The method uses amine and alcohol or two kinds of amines as the reaction materials, employs composite metal oxides catalyst at a reaction temperature of 80-180° C. to catalyze the reaction for 6-36 hours, so as to produce the N-substituted amine compound. The reaction condition of the method of the invention is relatively moderate, using a catalyst made of cheap non-noble metals, which is non-caustic and easy to be separated and reused. The reaction does not need any medium and has relatively high conversion rate and selectivity. 2. The method of claim 1 , wherein the molar ratio of Cu to Ni is from 10:1 to 1:10 claim 1 , and the molar ratio of Cu to Fe is from 10:1 to 1:10 in CuO—NiO—FeO.3. The method of claim 1 , wherein the molar ratio of Ni to Fe in NiO—FeOis from 10:1 to 1:10.4. The method of claim 1 , wherein the molar ratio of Cu to Fe in CuO—FeOis from 10:1 to 1:10.5. The method of claim 1 , wherein the molar ratio of Cu to Ni in CuO—NiO is from 10:1 to 1:10.6. (canceled)7. The method of claim 1 , wherein the mass ratio between the composite metal oxide catalyst and the amine is from 0.01:1 to 1.2:1.8. The method of claim 1 , wherein the composite metal oxide catalyst is produced by the following steps:{'sub': 3', '2', '3', '2', '3', '3', '3', '3, '1) adding an aqueous solution of any two or three nitrates selected from Cu(NO), Ni(NO), and Fe(NO), and an aqueous Al(NO)solution, to an aqueous alkali metal oxide or hydroxide solution, aqueous ammonia, or aqueous carbamide solution which functions as a precipitator to coprecipitate;'}2) after step 1), providing a crude catalyst by washing, drying in the air, calcining, and reducing in hydrogen gas;{'sub': 3', '4', '3', '4', '3', '4, '3) using an aqueous alkali metal hydroxide solution to remove any alumina in the crude catalyst obtained in steps 1) and 2) to provide a composite metal oxides catalyst CuO—NiO— ...

Process for producing ester compound

Compound (1) or a salt that is useful as an intermediate for the production of a medicine, an agrochemical or the like can be produced by a process including the following steps: (A) reacting an aldehyde (2) with nitromethane to produce a nitroaldehyde; (B) reacting the nitroaldehyde with an alcohol to produce a nitroacetal; (C) reducing the nitroacetal to produce an aminoacetal; (D) protecting an amino group in the aminoacetal to produce a protected aminoacetal; (E) treating the protected aminoacetal with an acid and subsequently with a base and then reacting the resultant product with a cyanating agent to produce a nitrile; (F) hydrolyzing the nitrile to produce a protected amino acid; and (G) substituting a group R 5 in the protected amino acid by a hydrogen atom and protecting a carboxyl group therein.

Process

The present invention relates to improved processes for the production of 2-amino-2-[2-(4-Calkyl-phenyl)ethyl]propane-1,3-diols, and to compounds for use therein. 7. A process according to claim 1 , wherein Ris n-hexyl.12. The process of claim 2 , which is performed on a continuous flow. The present invention relates to processes for the production of 2-amino-2-[2-(4-C-alkyl-phenyl)ethyl]propane-1,3-diols, and to compounds for use therein.2-Amino-2-[2-(4-C-alkyl-phenyl)ethyl]propane-1,3-diols are disclosed in EP-A-1627406 the relevant disclosure of which is incorporated herein by reference. On the basis of observed activity, the compounds have been found to be useful as immunosuppressants. Accordingly, the compounds may be useful in the treatment or prevention of acute allograft rejection, autoimmune diseases or xenograft rejection. A particular compound of this type is FTY720, i.e. 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, which has the following structure:FTY720 has been found to be useful in the prevention of autoimmune diseases, such as multiple sclerosis. FTY720 is the first-in-class sphingosine 1-phosphate (SIP) receptor modulator which has been effective in clinical trials for Multiple Sclerosis.WO 00/27798 discloses various processes for the preparation of 2-amino-2-[2-(4-C-alkyl-phenyl)ethyl]propane-1,3-diols. Some of these processes are illustrated in the reaction scheme below in relation to the production of FTY720, using the reference numerals given in the publication:The above processes involve formation of intermediate 18 via acylation of compound 16. However, the acylation process results in a mixture of ortho-, meta- and para-substituted products. None all these products have biological activity. There is a need for a processes for producing 2-amino-2-[2-(4-C-alkyl-phenyl)ethyl]propane-1,3-diols, in particular FTY720 and salts thereof, which have improved regioselectivity for the para-position of the benzene ring.Furthermore the above ...

IMPROVED METHOD FOR SYNTHESISING PARTIALLY N-HYDROXYETHYLATED TERTIARY 1,6-HEXANEDIAMINES

The invention relates to a synthesis method for at least one nitrogen compound belonging to the family of partly N-hydroxyethylated tertiary 1,6-hexanediamines with general formula (I) as follows: 3) A method as claimed in claim 1 , wherein the first precursor compound is 1 claim 1 ,6-hexanediamine and the second precursor compound 2 PET-3256 is ethylene oxide claim 1 , said method comprising:a first reaction step between the 1,6-hexanediamine and the ethylene oxide so as to form at least one intermediate compound selected from the list including N-(2-hydroxyethyl)-1,6-hexanediamine, N,N′-di(2-hydroxyethyl)-1,6-hexanediamine, N,N-di(2-hydroxyethyl)-1,6-hexanediamine and N,N,N′-tri(2-hydroxyethyl)-1,6-hexane-diamine;a second step of methylation of the primary or secondary amine functions of said at least one intermediate compound so as to form at least one compound according to general formula (I).4) A method as claimed in claim 3 , wherein the second methylation step is carried out by reaction between said intermediate compound claim 3 , formaldehyde and hydrogen in the presence of a hydrogenation catalyst claim 3 , or by reaction between said intermediate compound claim 3 , formaldehyde and formic acid according to the Eschweiler-Clarke reaction.5) A method as claimed in claim 3 , wherein the residual 1 claim 3 ,6-hexanediamine that has not reacted at the end of the first reaction step is recycled to said first reaction step claim 3 , after separation by distillation of said 1 claim 3 ,6-hexanediamine from said at least one intermediate compound.6) A method as claimed in claim 3 , wherein the molar ratio of ethylene oxide to 1 claim 3 ,6-hexanediamine is less than or equal to 3/1 claim 3 , and preferably less than or equal to 2.5/1.7) A method as claimed in claim 3 , further comprising claim 3 , at the end of the first reaction step claim 3 , at least one separation step claim 3 , preferably by distillation claim 3 , of at least one intermediate compound so as to ...

A PROCESS FOR THE PREPARATION OF 2-AMINO-1,3-PROPANE DIOL COMPOUNDS AND SALTS THEREOF

The present disclosure relates to processes for the preparation of 2-amino-1,3-propane diol compounds and their hydrochloride salts. Particularly, the present disclosure relates to processes for synthesizing 2-amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol and its hydrochloride salt 2-amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol hydrochloride respectively. The said process is safe, commercially feasible for large-scale synthesis and has improved efficacy along with many other advantages. The present disclosure also relates to the novel polymorphs of 2-amino-1,3-propane diol compound and its hydrochloride salt, where in 2-amino-1,3-propane diol compound is 2-amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol, and its hydrochloride salt is 2-amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol hydrochloride. 2. The process as claimed in claim 1 , wherein the reaction of step (a) is carried out in presence of solvent selected from a group comprising toluene claim 1 , xylene claim 1 , heptanes claim 1 , hexanes claim 1 , diethyl ether claim 1 , methyl tertiary butyl ether and tetrahydrofuran or any combination thereof; and further comprises adding reagent selected from a group comprising alkaline metal carbonate and alkaline earth metal carbonate or a combination thereof.3. The process as claimed in claim 2 , wherein volume of the solvent ranges from about 1 to about 30 volumes; and wherein the alkaline metal carbonate and alkaline earth metal carbonate is selected from a group comprising lithium carbonate claim 2 , sodium carbonate claim 2 , potassium carbonate claim 2 , cesium carbonate claim 2 , magnesium carbonate claim 2 , calcium carbonate and barium carbonate.4. The process as claimed in claim 1 , wherein the step (a) is carried out at temperature ranging from about 10° C. to about 160° C. and for a time period ranging from about 3 hours to about 24 hours.5. The process as claimed in claim 1 , wherein the conversion of step (b) or step (c) or step (d) is carried ...

PROCESS FOR PREPARING SUBSTITUTED PHENYLALKANES

The invention provides methods for preparing substituted phenylalkanes. In particular, the processes comprise reacting a phenyl boronic compound with an α-β unsaturated carbonyl-containing compound via an asymmetric 1,4-addition reaction. The processes may be useful in the synthesis of tapentadol. 2. The process of claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , or substituted alkyl; Ris alkyl or substituted alkyl; R claim 1 , R claim 1 , R claim 1 , and Rare independently hydrogen claim 1 , alkyl claim 1 , substituted alkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , substituted alkoxy claim 1 , aryl claim 1 , substituted aryl claim 1 , alkylaryl claim 1 , or substituted alkylaryl; Rand Rare independently alkyl or substituted alkyl; and Rand Rare independently hydrogen claim 1 , alkyl claim 1 , aryl claim 1 , or alkylaryl.3. The process of claim 2 , wherein Ris C-Calkyl; Ris C-Calkyl; R claim 2 , R claim 2 , R claim 2 , and Rare hydrogen; and R claim 2 , Rand Rare C-Calkyl.4. The process of claim 1 , wherein R is methyl; Ris hydrogen; Ris ethyl; each of R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen; and R claim 1 , R claim 1 , and Rare methyl.5. The process of claim 1 , wherein the compound of Formula (I) claim 1 , the compound of Formula (VIII) claim 1 , and the transition metal catalyst are present at a molar ratio of about 1:0.5:0.001 to about 1:2.0:0.05; and step (a) is conducted at a temperature from about −10° C. to about 80° C.6. The process of claim 5 , wherein the transition metal catalyst is a transition metal complex chosen from a rhodium complex claim 5 , a palladium complex claim 5 , or a ruthenium complex; the chiral ligand is a bicyclic chiral diene; and the transition metal catalyst and the chiral ligand are present at a weight ratio of about 1:0.1 to about 1:10.7. The process of claim 6 , wherein the compound of Formula (IX) is obtained with a diastereomeric excess of at least about 60%.8. The process of claim 6 , wherein step (a) ...

PROCESS FOR MANUFACTURING ETHYLENEAMINE COMPOUNDS

The present disclosure pertains to a process for manufacturing ethyleneamine compounds selected from the group of ethyleneamines and hydroxyethylethyleneamines wherein the process comprises two reaction sequences. 1. Process for manufacturing ethyleneamine compounds selected from the group of ethyleneamines and hydroxyethylethyleneamines wherein the process comprises a first and a second reaction sequences , in an adduction step, providing a CO2 adduct of a starting compound comprising a —NH—CH2-CH2-NH— moiety or a —NH—CH2-CH2-OH moiety, or HO—CH2-CH2-OH,', 'in a chain-extension step reacting a hydroxy-functional compound selected from ethanolamines and dihydroxyethane with an ethyleneamine compound, wherein at least part of a total of hydroxy-functional compounds and the ethyleneamine compound is provided in the form of a CO2 adduct, to form a CO2 adduct of a chain-extended ethyleneamine compound,', 'in an elimination step converting the CO2 adduct of the chain-extended ethyleneamine compound to the corresponding product ethyleneamine compound by removal of the carbonyl group, and, 'the first reaction sequence comprising the steps of in a ethylenedichloride reaction step reacting ethylenedichloride with at least one compound selected from the group of ammonia, an ethyleneamine and/or an ethanolamine to form a hydrochloride salt of the ethyleneamine and/or the ethanolamine,', 'in a caustic treatment step reacting a hydrochloride salt of the ethyleneamine or ethanolamine with a base to form an ethyleneamine compound and an inorganic chloride salt,', 'in a salt separation step separating the inorganic chloride salt from the ethyleneamine compound,, 'the second reaction sequence comprising the steps of effluent from a step in the first reaction sequence is provided as a starting material to a step in the second reaction sequence,', 'effluent from a step in the second reaction sequence is provided as a starting material to a step in the first reaction sequence,', 'a ...

NONIONIC SURFACTANT COMPOSITIONS

The present invention provides nonionic surfactants, compositions incorporating these surfactants, and related methods of making and using such surfactants and compositions. The nonionic surfactants demonstrate excellent equilibrium and dynamic surface tension properties as well as excellent wetting properties. Further, representative embodiments of the surfactants have shown low foaming characteristics, indicating that the surfactants would be suitable in applications where resistance to foaming is desired. The surfactants can be used singly or in combination with other nonionic and/or ionic surfactants as desired. As an over view, the nonionic surfactants of the present invention have a structure in which the surfactant backbone includes one or more amine moieties. At least one, preferably two or more branched, cyclic, fused cyclic, and/or spyro hydrophobic moieties are pendant from at least one of the amine moieties. Additionally, at least one, preferably two or more hydrophilic moieties, preferably alkylene oxide (i.e., polyether) chains also are pendant from at least one of the amine moieties. 1. A method of making a nonionic surfactant , comprising the steps of:a) providing an adduct comprising at least one secondary amine moiety and at least two branched, cyclic, fused cyclic, and/or spyro hydrophobic moieties; andb) N-functionalizing at least a portion of the secondary amine moieties of the adduct under conditions effective to convert at least a portion of the secondary amine moieties to tertiary amine moieties having pendant, hydrophilic, N-ether functionality.2. The method of claim 1 , wherein step (a) comprises reacting ingredients comprising first and second compounds under conditions effective to form the adduct claim 1 , wherein the first compound comprises one or more ketone and/or aldehyde moieties and the second compound comprises one or more primary amine moieties.3. The method of claim 2 , wherein the first compound comprises one or more of methyl ...

FLUORINE-CONTAINING ETHER MONOCARBOXYLIC ACID AMINOALKYL ESTER AND A METHOD FOR PRODUCING THE SAME

A fluorine-containing ether monocarboxylic acid aminoalkyl ester represented by the general formula: 2. The fluorine-containing ether monocarboxylic acid aminoalkyl ester according to claim 1 , wherein a is an integer of 4 to 10 claim 1 , and b is an integer of 1 to 3.4. The method for producing the fluorine-containing ether monocarboxylic acid aminoalkyl ester according to claim 3 , wherein after completion of the reaction claim 3 , the reaction mixture is treated with an alkali metal hydroxide aqueous solution. The present invention relates to a fluorine-containing ether monocarboxylic acid aminoalkyl ester and a method for producing the same. More particularly, the present invention relates to a fluorine-containing ether monocarboxylic acid aminoalkyl ester that is imparted with flexibility in a molecular chain due to an ether bond in a molecule, and that is effectively used as a synthetic raw material, etc.; and also relates to a method for producing the same.Heretofore, the present applicant has proposed various fluoroethers having a terminal alkylamino group, to which flexibility in the molecular chain is imparted by an ether linkage in the molecule, or fluorine-containing polyether carboxylic acid amides (see Patent Documents 1 to 7). Further, the present applicant has also proposed fluorine-containing acid fluoride compounds having COOH, CONH, or the like at the molecular end (see Patent Document 8).However, there has been hardly observed finding on fluorine-containing ether carboxylic acid esters having an amino group at the end of the ester group.Patent Document 1: WO 2007/026513Patent Document 2: JP-A-2008-255042Patent Document 3: JP-A-2009-1709Patent Document 4: JP-A-2010-254736Patent Document 5: JP-A-2011-202055Patent Document 6: JP-A-2011-213837Patent Document 7: JP-A-2013-32455Patent Document 8: JP-A-2008-255035Patent Document 9: JP-A-3-284642Patent Document 10: JP-A-62-270546An object of the present invention is to provide a fluorine-containing ether ...

Compounds as ppar beta/delta inhibitors for treating ppar beta/delta-mediated diseases

The present invention concerns substances which act as selective ligands of nuclear receptors of the PPAR beta/delta subtype and which can be used for the treatment of PPAR beta/delta-mediated diseases. The substances of this invention act as inhibitors of PPAR beta/delta receptors.

PROCESS FOR PRODUCING N-METHYL OR N,N-DIMETYL AMINES

A process for producing N-methyl or N,N-dimethyl amines, which comprises using amine compound, nitro-containing compound or nitrile compound as a starting material, carbon dioxide as a methylating agent and hydrogen gas as a reducing agent, and allowing them to react in a sealed reactor for 6 to 48 h in a reaction medium at a reaction temperature of 80 to 180 ° C. in the presence of a composite catalyst, so as to provide N-methyl or N,N-dimethyl amines. The process of the present invention is simple and under relative mild reaction conditions. By means of the process of the invention, the target products can be prepared at low cost with a high yield. The catalysts used have a high catalytic activity and can be separated from the reaction system simply and reused. Furthermore, the whole process of the present invention is environmental-friendly and facilitates the cycling use of carbon dioxide. 1. A process for producing N-methyl or N ,N-dimethyl amines comprisingusing amine compound, nitro-containing compound or nitrile compound as a starting material, carbon dioxide as a methylating agent, and hydrogen gas as a reducing agent, and allowing them to react in a reaction medium in a sealed reactor for 6 to 48 h at a reaction temperature of 80 to 180° C. in the presence of a composite catalyst, to provide the N-methyl or N,N-dimethyl amines,wherein the composite catalyst is formed of oxides of at least two metals, or of oxide of at least one metal and at least another metal element, said metal or metal element is selected from the group consisting of aluminum, bismuth, zinc, tin, gold, silver, copper, nickel, palladium, platinum, iridium, rhodium, cobalt, iron, ruthenium, osmium, manganese, rhenium, chromium, molybdenum, tungsten, vanadium, titanium, zirconium, lanthanum, yttrium, cerium, magnesium, calcium and barium.2. The process according to claim 1 , wherein the molar ratio of the methylating agent to the starting material is 1:1˜20:1 and the molar ratio of the ...

Salts of diaminoacetals and diaminoketals and their synthesis, and their transformations to diaminoacetals and diaminoketals

This application relates, in part, to novel salts represented by the following structure of Formula (1): wherein R 1a is selected from the group consisting of hydrogen and optionally substituted alkyl (e.g., unsubstituted C 1-6 alkyl, e.g., —CH 3 ); R 1b is optionally substituted alkyl (e.g., unsubstituted C 1-6 alkyl, e.g., —CH 3 ); each occurrence of R 2 and R 3 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted aryl; R 2 and R 3 can combine with each other to form optionally substituted cycloalkyl; each m and n is independently an integer ranging from 1 to 20 (e.g., m and n is independently an integer ranging from 1 to 5); and each of Q 1 ⊖ and Q 2 ⊖ is independently a counterion (e.g., each of Q 1 ⊖ and Q 2 ⊖ is independently a counterion selected from the group consisting of chloride, bromide, fluoride, iodide, acetate, carboxylate, hydrogen sulfate, nitrate, and phenolate, and sulfonate, e.g., chloride), and methods of making the same.

Catalytic Process For Preparing N,N-Dimethylglucamine From N Methylglucamine

The invention relates to a method for preparing aqueous solutions of N,N-dimethylglucamine, characterized by first preparing an adduct of N-methylglucamine and formaldehyde in water at temperatures of between 15° C. and 40° C., and subsequently reacting said adduct to N,N-dimethylglucamine in the presence of a metal catalyst under hydrogen pressure at 20-68° C., followed by secondary hydrogenation at 70-120 bar and 70-110° C. once hydrogen absorption at 20-68° C. is completed. 1. A process for preparing N ,N-dimethylglucamine comprising the step of reacting an aqueous solution of N-methylglucamine first with an aqueous solution of formaldehyde at 15-40° C. and subsequently , at a pressure of 20-120 bar and a temperature T=30-68° C. , with hydrogen under metal catalysis , wherein , after absorption of hydrogen has completed at 20-68° C. , a further , after-hydrogenation is added at 70-120 bar and at 70-110° C.2. The process as claimed in claim 1 , wherein the metal catalyst is Raney nickel.3. The process as claimed in claim 1 , which is carried out at a hydrogen pressure of 70-110 bar.4. The process as claimed in claim 1 , wherein the hydrogenation is carried out at 35-65° C.5. The process as claimed in claim 1 , wherein the molar ratio of N-methylglucamine to formaldehyde is 1:1 to 1:1.5.6. The process as claimed in claim 1 , wherein the hydrogenation catalyst is reused more than 5 times.7. The process as claimed in claim 1 , wherein reaction takes place in a stirred reactor or loop reactor.8. The process as claimed in claim 1 , wherein the remaining N-methylglucamine content is <2 claim 1 , wt %.9. The process as claimed in claim 1 , wherein the residual formaldehyde content is <0.1 wt %.10. The process as claimed in claim 1 , in which the Hazen color number of the resulting solution of N claim 1 ,N-dimethylglucamine is <500.11. The process as claimed in claim 1 , in which the molar ratio of N-methylglucamine to formaldehyde is 1:1 to 1:1.2.12. The process as ...

Method for Preparation of Fluoro Alkylated Compounds by Homogeneous NI Catalysis

The invention discloses a method for the preparation of fluoro alkylated compounds by homogeneous Ni catalyzed fluoro alkylation with fluoro alkyl halides in the presence of a base. 2. The method according to claim 1 , wherein{'sub': '3', 'LIG is compound of formula (DPEPhos) or PhP.'}3. The method according to claim 1 , wherein{'sub': 2', '3', '3', '4, 'BAS is selected from the group consisting of CsCO, KPO, NaH and NaOtBu.'}5. The method according to claim 1 , wherein by 1, 2 or 3 in case of COMPSUBST-I being a monocyclic compound with 5 endocyclic atoms,', 'by 1, 2, 3, 4 or 5 in case of COMPSUBST-I being a monocyclic compound with 6 endocyclic atoms,', 'by 1, 2, 3 or 4 in case of COMPSUBST-I being a bicyclic compound wherein a 5-membered and a 6-membered ring are ortho-fused,', 'by 1, 2, 3, 4 or 5 in case of COMPSUBST-I being a bicyclic compound wherein two 6-membered rings are ortho-fused,, 'COMPSUBST-I is unsubstituted or substituted'}{'sub': 1-4', '3', '2', 'm', '2, 'identical or different substituents independently from each other selected from the group consisting of Calkyl, CM alkoxy, OH, C(H)═O, N(R10)R11, CN, F, Cl, Br, CF, (CH)—C(O)Y1, and S(O)R50;'}{'sub': '1-4', 'said Calkyl substituent of COMPSUBST-I is unsubstituted or substituted with 1, 2 or 3 identical or different substituents selected from the group consisting of halogen;'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'with R10, R11, m, Y1, R50 and halogen as defined in .'}7. The method according to claim 1 , wherein{'sub': 1-20', '2', 'n3', '2, 'FAHALIDE is selected from the group consisting of perfluoro Calkyl-X1, Br—(CF)—Br, and FHC—X1;'}with n3 being an integer of 2 to 10.8. The method according to claim 1 , whereinn3 is 2, 3, 4, 5, 6.9. The method according to claim 1 , wherein{'sub': 21', '10', '21', '10', '17', '8', '17', '8', '13', '6', '13', '6', '9', '4', '9', '4', '7', '3', '7', '3', '3', '3', '2', '4', '2', '2, 'FAHALIDE is selected from the group consisting of FC—I, FC—Br, FC—I, ...

AMINE FOR LOW-EMISSION EPOXY RESIN PRODUCTS

The present invention relates to an amine of the formula (I) which is an adduct of 1,2-propylenediamine with an aryl monoglycidyl ether, to the use thereof as part of a hardener for epoxy resins, and to epoxy resin compositions obtained therewith. The amine of the formula (I) is preparable in a simple process in high purity, is of very low viscosity and is especially suitable for the curing of epoxy resins. It allows low-emission epoxy resin compositions which have good workability and which cure even under cold and damp conditions, quickly and without blushing effects, to form very hard products of high surface quality that display virtually no yellowing on exposure to light. 2. The amine as claimed in claim 1 , wherein n is 1.3. The amine as claimed in claim 1 , wherein R is methyl.4. A process for preparing an amine as claimed in by reacting 1 claim 1 ,2-propylenediamine with an aryl glycidyl ether in a 1 claim 1 ,2-propylenediamine/aryl glycidyl ether molar ratio in the range from 1.1 to 5 and subsequent distillative removal of unreacted 1 claim 1 ,2-propylenediamine.5. A method wherein at least one amine as claimed in is used in a hardener for epoxy resins.6. The method as claimed in claim 5 , wherein the hardener comprises an amine of formula (I) in an amount such that 5 to 100% of the amine hydrogens in the hardener that are reactive toward epoxide groups originate from the amine of the formula (I).7. The method as claimed in claim 5 , wherein the hardener as well as the amine of the formula (I) comprises at least one further polyamine having at least two amine hydrogens that are active toward epoxide groups.8. The method as claimed in claim 7 , wherein the further polyamine is a primary diamine selected from the group consisting of 2 claim 7 ,2 claim 7 ,4- and 2 claim 7 ,4 claim 7 ,4-trimethylhexamethylenediamine claim 7 , 1-amino-3-aminomethyl-3 claim 7 ,5 claim 7 ,5-trimethylcyclohexane claim 7 , 1 claim 7 ,3-bis(aminomethyl)benzene claim 7 , 1 claim 7 ,3- ...

ANTIMUSCARINIC COMPOUND HAVING A LOW CONTENT OF IMPURITIES

Substantially stable to degradation Fesoterodine fumarate, a process for its preparation and a process for the synthesis of specific degradation impurities of Fesoterodine fumarate are disclosed. 1. A process for the preparation of a substantially stable to degradation Fesoterodine fumarate , comprising:the salification of Fesoterodine base with fumaric acid in the presence of a solvent wherein the molar ratio between Fesoterodine base and fumaric acid is comprised between about 1:0.10 and about 1:0.88;the precipitation of Fesoterodine fumarate from the resulting solution;the recovery of the solid.2. Process according to wherein the Fesoterodine base to fumaric acid molar ratio is comprised between about 1:0.5 and about 1:0.85.4. Process according to wherein the molar ratio of the compound of formula (IV) to fumaric acid is comprised between about 1:0.4 and about 1:0.80.6. A substantially stable to degradation Fesoterodine fumarate as obtainable according to the process of .7. Fesoterodine fumarate according to claim 5 , having a total content of the impurities of formula (VI) claim 5 , (VII) (VIII) or (IX) equal to or lower than 0.1% claim 5 , and preferably comprised between about 0.1% and about 0.01% claim 5 , calculated as Area % by HPLC.8. A pharmaceutical composition comprising substantially stable to degradation Fesoterodine fumarate according to and a pharmaceutically acceptable carrier and/or excipient.9. A substantially stable to degradation Fesoterodine fumarate claim 5 , according to claim 5 , for use as a medicament claim 5 , in particular in a method of treatment of urinary incontinence in a mammal in need thereof. The invention relates to a process for the preparation of (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)phenol isobutyrate (Fesoterodine) as fumarate salt, substantially stable as herein defined, that is Fesoterodine fumarate which substantially does not develop degradation impurities; and a method for the preparation of ...

BIS(PHOSPHINE)-CARBODICARBENE CATALYST COMPLEXES AND METHODS OF USING THE SAME

An organometallic complex of a tridentate bis(phosphine)-carbodicarbene ligand and a transition metal, is described. In some embodiments the ligand has the structure of Formula (I): The complexes are useful in methods of making an allylic amine carried out by reacting a 1,3-diene with a substituted amine in the presence of such an organometallic complex to produce by intermolecular hydroamination the allylic amine. 1. An organometallic complex , comprising:(a) a tridentate bis(phosphine)-carbodicarbene ligand, and(b) a transition metal.4. The complex of claim 1 , wherein said transition metal is selected from the group consisting of ruthenium claim 1 , nickel claim 1 , palladium claim 1 , platinum claim 1 , rhodium claim 1 , iridium claim 1 , cobalt claim 1 , iron claim 1 , silver claim 1 , gold claim 1 , and molybdenum.5. The complex of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare each independently selected alkyl or aryl.6. The complex of claim 2 , wherein at least one R′ is S-L- claim 2 , where S is a solid support and L is a linking group.7. The complex of claim 2 , wherein each R′ is independently hydrogen claim 2 , halo claim 2 , loweralkyl claim 2 , loweralkoxy claim 2 , or hydroxyl.8. A reaction mixture comprising an organometallic complex of claim 1 , a solvent claim 1 , a 1-3 claim 1 , diene substrate claim 1 , and a substituted amine substrate.11. A method of making an allylic amine claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'reacting a 1,3-diene with a substituted amine in the presence of an organometallic complex of in a catalytic amount to produce by intermolecular hydroamination said allylic amine.'}14. A tridentate bis(phosphine)-carbodicarbene pincer ligand. This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/979,749, filed Apr. 15, 2014, the disclosure of which is incorporated by reference herein in its entirety.The present invention concerns carbodicarbene ligands, ...

SYNTHESIS OF NOVEL IONIC LIQUIDS FROM LIGNIN-DERIVED COMPOUNDS

Methods and compositions are provided for synthesizing ionic liquids from lignin derived compounds comprising: contacting a starting material comprising lignin with a depolymerization agent to depolymerize the lignin and form a mixture of aldehyde containing compounds; contacting the mixture of aldehyde containing compounds with an amine under conditions suitable to convert the mixture of aldehyde containing compounds to a mixture of amine containing compounds; and contacting the mixture of amine containing compounds with an acid under conditions suitable to form an ammonium salt, thereby preparing the ionic liquid. 1. A process for preparing an ionic liquid comprising:contacting a starting material comprising lignin with a depolymerization agent to depolymerize the lignin and form a mixture of aldehyde containing compounds;contacting the mixture of aldehyde containing compounds with an amine under conditions suitable to convert the mixture of aldehyde containing compounds to a mixture of amine containing compounds; andcontacting the mixture of amine containing compounds with an acid under conditions suitable to form an ammonium salt, thereby preparing the ionic liquid.2. The method of claim 1 , wherein the step of contacting the starting material with a depolymerization agent comprises contacting the starting material with one or more compositions selected from the group consisting of an ionic liquid; hydrogen gas; a hydrogen donating agent selected from the group consisting of tetralin claim 1 , sodium formate and formic acid; a dilute acid; a concentrated acid; a base; a catalyst and an oxidizing agent selected from the group consisting of nitrobenzene claim 1 , metal oxides claim 1 , hydrogen peroxide claim 1 , and oxygen gas; Fenton's reagent; metal organic frameworks of copper or iron; and ammonium hydroxide.3. The method of claim 2 , wherein the depolymerization agent comprises a lignin-derived ionic liquid.4. The method of claim 2 , wherein the ...

COMPOSITION CONTAINING 3-CHLORO-4-METHOXYBENZYLAMINE HYDROCHLORIDE, AND METHOD FOR PRODUCING SAME

There is provided a method for producing, at a high yield, a composition containing 3-chloro-4-methoxybenzylamine hydrochloride (CMBA-HCl) in which the purity of CMBA-HCl is high. This method comprises a chlorination step involving a chlorination reaction that generates CMBA-HCl from 4-methoxybenzylamine hydrochloride using hydrogen peroxide and hydrochloric acid. There is also provided a CMBA-HCl-containing composition which is produced by the aforementioned production method and in which the purity of CMBA-HCl is high. 1. A method for producing a composition containing 3-chloro-4-methoxybenzylamine hydrochloride , the method comprising a chlorination step involving a chlorination reaction that generates 3-chloro-4-methoxybenzylamine hydrochloride from 4-methoxybenzylamine hydrochloride using hydrogen peroxide and hydrochloric acid.2. A method for producing a composition containing 3-chloro-4-methoxybenzylamine hydrochloride , the method comprising a purification step of recrystallizing a composition containing 3-chloro-4-methoxybenzylamine hydrochloride using a solvent containing a tertiary amine.3. A method for producing a composition containing 3-chloro-4-methoxybenzylamine hydrochloride , the method comprising:a chlorination step involving a chlorination reaction that generates 3-chloro-4-methoxybenzylamine hydrochloride from 4-methoxybenzylamine hydrochloride using hydrogen peroxide and hydrochloric acid; anda purification step of recrystallizing a generated product obtained by the chlorination step, using a solvent containing a tertiary amine.4. The method for producing as recited in claim 1 , wherein a starting material for the chlorination reaction is a composition containing 4-methoxybenzylamine hydrochloride and a content of the 4-methoxybenzylamine hydrochloride is 99.5% or more as a content based on a peak area ratio obtained by HPLC measurement.5. The method for producing as recited in claim 2 , wherein the purification step includes reducing a content ...

SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

Provided are immediate or prolonged administration of certain salts of Kchannel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving Kchannels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals. 1129.-. (canceled)130. A method of treatment of a subject suffering from or at risk for Alzheimer's disease , said method comprising administering to said subject a therapeutically effective amount of a pharmaceutical formulation comprising a Kchannel opener.131. A kit comprising instructions and a crystalline form B of 7-chloro-3-methyl-2H-1 ,2 ,4-benzothiadiazine dioxide:2-hydroxy-N ,N ,N-trimethyl ethanaminium (1:1) salt having characteristic peaks in a XRPD pattern substantially as shown in .132. The kit of claim 131 , wherein the crystalline form B has characteristic infrared absorbances at 3256 claim 131 , 2174 claim 131 , 2890 claim 131 , 1605 claim 131 , 1463 claim 131 , and 1235 cm.133. The kit of claim 131 , wherein the characteristic peaks comprise two-theta peaks (Cu Kα claim 131 , 40 kV claim 131 , 40 mA) at approximately 10.3 claim 131 , 18.3 claim 131 , 20.6 claim 131 , and 26.3 degrees.134. The kit of claim 131 , wherein the characteristic peaks comprise two-theta peaks (Cu Kα claim 131 , 40 kV claim 131 , 40 mA) at approximately 8.9 claim 131 , 12.0 claim 131 , 24.1 claim 131 , 24.5 claim 131 , 27.1 claim 131 , and 28.9 degrees.135. The kit of claim 131 , wherein the crystalline form B has an NMR spectrum substantially as shown in .136. The kit of claim 135 , wherein the crystalline form B has characteristic chemical shifts in an NMR spectrum (DMSO-d6 ...

PROCESS TO PREPARE TREPROSTINIL, THE ACTIVE INGREDIENT IN REMODULIN®

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil. 1. A pharmaceutical batch of a salt of treprostinil that can be stored as a stable compound at ambient temperature and that is prepared by a method comprising (a) alkylating a benzindene triol , (b) hydrolyzing the product of step (a) to form a solution comprising treprostinil , and (c) contacting the solution comprising treprostinil from step (b) with a base to form a salt of treprostinil , wherein forming the salt of step (c) reduces the amount of one or more impurities resulting from steps (a) and/or (b) in the pharmaceutical batch , said pharmaceutical batch being at least 2.9 grams.2. The pharmaceutical batch of claim 1 , wherein the method further comprises converting the salt of treprostinil to treprostinil by acidification.3. The pharmaceutical batch of claim 1 , wherein the pharmaceutical batch has been dried under vacuum.4. The pharmaceutical batch of claim 1 , wherein the base is diethanolamine.5. A pharmaceutical product comprising a carrier and a therapeutically effective amount of a salt of treprostinil claim 1 , wherein the salt of treprostinil is from a pharmaceutical batch as claimed in .6. A pharmaceutical product comprising a carrier and a therapeutically effective amount of treprostinil claim 2 , wherein the treprostinil is from a pharmaceutical batch as claimed in .7. The pharmaceutical product of claim 5 , wherein the salt is the diethanolamine salt of treprostinil.8. A method of preparing a pharmaceutical product from a pharmaceutical batch as claimed in claim 5 , comprising storing a pharmaceutical batch of a salt of treprostinil as claimed in at ambient temperature and preparing a pharmaceutical product from the pharmaceutical batch after storage.9. A method as claimed in claim 8 , wherein the salt of ...

RADIOLABELING AGENTS, METHODS OF MAKING, AND METHODS OF USE THEREOF

Described herein are labeling agents, specifically [C]fluoroform, [C]difluoromethane, [C]fluoromethyl iodide, [C]fluoromethyl bromide, [C]fluoromethyl chloride, [C]fluoromethyl trifluoromethansulfonate, [C]difluoromethyl iodide, [C]difluoromethyl bromide, [C]difluoromethyl chloride, [C]difluoromethyl trifluoromethansulfonate, [C]trifluoromethyl iodide, [C]trifluoromethyl bromide, [C]trifluoromethyl chloride, [C]trifluoromethyl trifluoromethansulfonate, []fluoroform, [F]difluoromethane, [F]difluoromethyl bromide or [F]trifluoromethyl bromide. Also included are methods of labeling precursors to provide labeled fluoroalkanes and imaging methods. 1. A gas phase solvent-free method for producing an C- or F-labeled fluoroalkane , the method comprising{'sup': 11', '18', '18', '11', '11, 'sub': 11', '11', '3, 'contacting [C]methane, [F]fluoromethane, [F]fluoromethyl bromide, [C]methyl iodide, [C]methyl bromide, [C]methyl chloride, or [C]methyl trffluoromethansuifonate, with CoFat a temperature of 50 to 450° C., and'}{'sup': 11', '18, 'isolating the C- or F-labeled fluoroalkane that is produced.'}2. The method of claim 1 , wherein{'sup': 11', '11, 'the precursor is [C]methane and the labeled fluoroalkane is [C]fluoroform,'}{'sup': 18', '18, 'the precursor is [F]fluoromethane and the labeled fluoroalkane is [F]fluoroform,'}{'sup': 18', '18, 'the precursor is [F]fluoromethane and the labeled fluoroalkane is [F]difluoromethane,'}{'sup': 18', '18, 'the precursor is [F]fluoromethyl bromide and the labeled fluoroalkane is [F]difluoromethyl bromide,'}{'sup': 18', '18, 'the precursor is [F]fluoromethyl bromide and the labeled fluoroalkane is [F]trifluoromethyl bromide,'}{'sup': 11', '11, 'the precursor is [C]methyl iodide and the labeled fluoroalkane is [C]fluoromethyl iodide,'}{'sup': 11', '11, 'the precursor is [C]methyl bromide and the labeled fluoroalkane is [C]fluoromethyl bromide,'}{'sup': 11', '11, 'the precursor is [C]methyl chloride and the labeled fluoroalkane is [C] ...

METHODS FOR THE PREPARATION OF HIV ATTACHMENT INHIBITOR PIPERAZINE PRODRUG COMPOUND

A method for making the compound 2. The process of claim 1 , wherein said first solvent is selected from the group of NMP claim 1 , DMSO claim 1 , MeCN claim 1 , MeOH claim 1 , acetone and a carboxylic acid.3. The process of claim 1 , wherein said second solvent is selected from the group of an alkyl ketone claim 1 , heptane claim 1 , toluene claim 1 , and ethyl acetate.4. The process of claim 1 , wherein the first solvent is acetic acid claim 1 , and said second solvent is acetone. This application is a divisional application of U.S. Ser. No. 13/760,526 filed Feb. 6, 2013, now allowed, which claims the benefit of U.S. Provisional Application Ser. No. 61/596,362 filed Feb. 8, 2012, which is herein incorporated by reference in its entirety.The invention relates to methods of making HIV attachment inhibitor compounds useful as antivirals, and in particular, to methods of making the piperazine prodrug compound identified as 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-piperazine. The invention also relates to the compounds, including intermediates, obtained by the processes herein set forth.HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with tens of millions of people still infected worldwide at the end of 2011. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2005, for example, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the treatment of HIV include nucleoside reverse transcriptase (RT) inhibitors or approved single pill combinations: zidovudine (or AZT or RETROVIR®), didanosine (or VIDEX®), stavudine (or ZERIT®) lamivudine (or 3TC or EPIVIR®), zalcitabine (or DDC or HIVID®), abacavir succinate (or ZIAGEN®), Tenofovir disoproxil fumarate salt (or VIREAD®), emtricitabine (or FTC or EMTRIVA®), COMBIVIR® (contains −3TC plus ...

Composition containing 3-chloro-4-methoxybenzylamine hydrochloride, and method for producing same

There is provided a method for producing, at a high yield, a composition containing 3-chloro-4-methoxybenzylamine hydrochloride (CMBA-HCl) in which the purity of CMBA-HCl is high. This method comprises a chlorination step involving a chlorination reaction that generates CMBA-HCl from 4-methoxybenzylamine hydrochloride using hydrogen peroxide and hydrochloric acid. There is also provided a CMBA-HCl-containing composition which is produced by the aforementioned production method and in which the purity of CMBA-HCl is high.

Process and intermediates for the production of 17(20)-ene b-seco steroids

The invention pertains to a process for producing a compound of formula (11) wherein R7 and R8 are each independently selected from H, halogen, alkyl, aryl, or alkylaryl, R42 is H or a protective group, R43 is H or R3, wherein R3 is a protective group, by contacting a compound of formula (10) with an olefmation reagent, wherein compound of formula (10) comprises a counter acid X1 when R42═H and R43═H.

PHARMACEUTICALLY ACCEPTABLE AMINE SALTS OF PITAVASTATIN

The present invention relates to pharmaceutically acceptable amine salts of pitavastatin and a method for producing pharmaceutically acceptable amine salts of pitavastatin. Also provided are pharmaceutical compositions of these amine salts or solvates thereof, and methods of their use as HMG-CoA reductase inhibitors. 1. A pharmaceutically acceptable amine salt of pitavastatin , wherein said amine is selected from the group consisting of aminopolyols and tetraalkyl ammonium salts.2. The pharmaceutically acceptable amine salt of pitavastatin of wherein said aminopolyol is tromethamine.3. The pharmaceutically acceptable amine salt of pitavastatin of wherein said tetraalkyl ammonium salt is choline.4. A method for the preparation of an amine salt of pitavastatin comprising reacting pitavastatin acid or pitavastatin calcium salt with an amine in a solvent followed by precipitating said amine salt of pitavastatin claim 1 , wherein said reacting is carried out at a first temperature and said precipitating is carried out at a second temperature that is at least 5° C. below said first temperature.6. Method according to wherein said amine is selected from the group consisting of amino acids claim 4 , aminopolyols claim 4 , amino sugars claim 4 , ammonia claim 4 , ethyl amine derivatives claim 4 , guanines claim 4 , purines claim 4 , tetraalkyl ammonium salts and vitamins.7. Method according to wherein said amine is an amino acid selected from the group consisting of histidine claim 6 , lysine and ornithine.8. Method according to wherein said amine is tromethamine.9. Method according to wherein said amine is an amino sugar selected from the group consisting of daunosamine claim 6 , galactosamine claim 6 , glucosamine and N-methylglucamine.10. Method according to wherein said amine is an ethyl amine derivative selected from the group consisting of benzathine claim 6 , diethyl amine claim 6 , ethanol amine claim 6 , ethyl amine claim 6 , ethylene diamine claim 6 , 1-(2- ...

A PROCESS FOR PREPARING BETA AGONIST

Disclosed is a process for preparing β-agonist, 1-(4-amino-3,5-dichlorophenyl)-2-(tert-butylamino) ethanol, of Formula I. The process comprises refluxing 1-(4-amino-3,5-dichlorophenyl) ethanone of Formula II and selenium dioxide in the presence of 1,4-dioxane to form compound of Formula III. Further, compound of Formula III is heated at a temperature below 30° C. in the presence of t-butyl amine to form compound of Formula IV. The compound of Formula IV is treated with sodium borohydride to form compound of Formula I. 2. The process as claimed in claim 1 , wherein the predefined temperature in step c) is in a range of 25° C.-30° C.4. The process as claimed in claim 3 , wherein the predefined temperature in step a) is in a range of 25° C.-70° C.5. The process as claimed in claim 3 , wherein the alcohol used in step a) is isopropyl alcohol.6. The process as claimed in claim 3 , wherein the predefined temperature in step b) is below 30° C.7. The process as claimed in claim 3 , wherein the predefined pH in step b) is in a range of 10-12.9. The process as claimed in claim 8 , wherein the predefined temperature is in a range of 60°-70° C.10. The process as claimed in claim 8 , the predefined pH is in a range of 6-6.5.11. The process as claimed in claim 8 , wherein the solvent is selected from isopropyl alcohol and toluene claim 8 , preferably isopropyl alcohol. The invention relates to a process for preparing β agonist and more particularly, to a process for preparation of Clenbuterol and salts thereof.β-agonists are a class of sympathomimetic agents which act upon the β adrenoceptors that relax muscles of the airways and results in easier breathing.Clenbuterol (CL) is an extremely potent β-agonist with preferential affinity for β2-adrenoceptor of the bronchial and uterine smooth muscle. Clinical trials have however revealed that the selectivity of CL for bronchodilation is not absolute and even at “therapeutic doses” this β-agonist can activate β1-adrenoceptors in the ...

PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY AND NOVEL INTERMEDIATES AND METHODS RELATED THERETO

The present disclosure pertains to peptide nucleic acid (PNA) monomers and oligomers, as well as methods and compositions useful for the preparation of PNA monomer precursors (e.g. PNA Monomer Esters, Backbone Esters and Backbone Ester Acid Salts, as described below) that can be used to prepare PNA monomers wherein said PNA monomers can be used to prepare said PNA oligomers. In some embodiments, the disclosure features sulfonic acid salts of Backbone Ester compounds, which sulfonic acid salts generally tend to be crystalline and can be obtained in reasonably good yield, often without requiring any chromatographic purification of the reaction product of the Backbone Ester synthesis reaction. This disclosure also pertains to novel methods for the synthesis of said Backbone Ester compounds and novel methods for the formation of the related sulfonic acid salts. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethy-(TCE), 2,2,2-tribromoethyl-(TBE), 2-iodoethyl-groups (2-IE) and 2-bromoethyl-(2-BrE) as the ester group. These particular ester groups can be removed under conditions where both Boc and Fmoc protected amine groups are stable. 23-. (canceled)4. The compound of claim 1 , wherein Y is selected from benzenesulfonate claim 1 , p-toluenesulfonate claim 1 , naphthalenesulfonate claim 1 , p-xylene-2-sulfonate claim 1 , 2 claim 1 ,4 claim 1 ,5-trichlorobenzenesulfonate claim 1 , 2 claim 1 ,6-dimethylbenzenesulfonate claim 1 , 2-mesitylenesulfonate claim 1 , 2-mesitylenesulfonate dihydrate claim 1 , 2-methylbenzene sulfonate claim 1 , 2-ethylbenzenesulfonate claim 1 , 2-isopropylbenzenesulfonate claim 1 , 2 claim 1 ,3-dimethylbenzenesulfonate claim 1 , 2 claim 1 ,4 claim 1 ,6-trimethylbenzenesulfonate claim 1 , and 2 claim 1 ,4 claim 1 ,6-triisopropylbenzenesulfonate.5. The compound of claim 1 , wherein Y is p-toluenesulfonate.67-. (canceled)8. The compound of claim 1 , wherein Ris H or D.911-. (canceled)12. The compound of claim 1 , wherein Pgis ...

PROCESS FOR PRODUCING AN AMINOPROPYNE OR ENAMINONE

There is provided a process for producing an aminopropyne or an enaminone comprising the step of reacting a metal acetylide, an amine and a carbonyl-containing compound in the presence of a transition metal catalyst. There is also provided a process for producing an aminopropyne comprising the step of reacting a metal acetylide, an amine and a halide-containing compound in the presence of a transition metal catalyst at a reaction temperature of 50° C. to 150° C. There are also provided processes to further synthesize the aminopropyne produced to obtain a butyneamine, another aminopropyne or a triazol. 1. A process for producing an aminopropyne comprising the step of reacting a metal acetylide , an amine and a carbonyl-containing compound in the presence of a transition metal catalyst.2. The process as claimed in claim 1 , wherein said aminopropyne has a terminal alkyne group.3. The process as claimed in claim 1 , wherein said metal acetylide has the structure MC claim 1 , where M is a metal selected from the group consisting of an alkali metal claim 1 , an alkaline earth metal and a transition metal; or wherein said metal acetylide is selected from the group consisting of calcium carbide (CaC) claim 1 , lithium acetylide (LiC) and lanthanium acetylide (LaC).4. (canceled)5. The process as claimed in claim 1 , wherein the transition metal of said transition metal catalyst is selected from the group consisting of copper claim 1 , silver and gold; wherein the copper catalyst is selected from the group consisting of copper chloride claim 1 , copper bromide claim 1 , copper iodide claim 1 , copper fluoride claim 1 , copper acetate and copper acetylacetonate.6. (canceled)7. The process as claimed in claim 1 , wherein said carbonyl-containing compound is an aldehyde having the structure RCHO claim 1 , where Ris selected from aryl or C-alkyl claim 1 , said aryl being optionally substituted by at least one of halide claim 1 , nitrile claim 1 , C-alkyl claim 1 , C-alkoxide ...

METHODS FOR PREPARING AMMONIUM TETRATHIOMOLYBDATE

This disclosure relates to crystalline ammonium tetrathiomolybdate having pharmaceutical grade purity and processes for manufacturing crystalline ammonium tetrathiomolybdate. This disclosure also relates to processes for manufacturing bis-choline tetrathiomolybdate having pharmaceutical grade purity. 1. A process for manufacturing crystalline ammonium tetrathiomolybdate (ATTM) , the process comprising:contacting a molybdenum compound selected from ammonium heptamolybdate, ammonium dimolybdate, sodium molybdate, molybdenum oxide, and hydrate thereof with water and ammonia in a reaction vessel under stirring to obtain a molybdenum compound solution;providing ammonium sulfide to the molybdenum compound solution in an amount corresponding to a S:Mo molar ratio in a range of 4.5:1 to 6.5:1 over a period of time sufficient to obtain a reaction mixture;maintaining the reaction mixture at a temperature in a range of 35° C. to 55° C. for a reaction time of at least 4 hours to create a slurry;optionally providing a crystallization solvent to the slurry;optionally maintaining the slurry at a temperature in a range of 10° C. to 30° C. for at least 2 hours; andremoving liquid from the slurry to obtain crystalline ATTM.2. The process of claim 1 , wherein the molybdenum compound is selected from ammonium heptamolybdate claim 1 , ammonium dimolybdate claim 1 , sodium molybdate claim 1 , and hydrate thereof.3. The process of claim 1 , wherein the molybdenum compound is ammonium heptamolybdate or ammonium heptamolybdate tetrahydrate.4. The process of claim 1 , wherein the molybdenum compound is ammonium dimolybdate.5. The process of any one of - claim 1 , wherein ammonium sulfide is provided in an amount corresponding to a S:Mo molar ratio in a range of 4.5:1 to 6.2:1.6. The process of any one of - claim 1 , wherein the period of time sufficient to obtain a reaction mixture is at least 15 minutes.7. The process of any one of - claim 1 , wherein the reaction mixture is maintained at a ...

METHOD FOR PRODUCING AN ARENE WITH AN AROMATIC C-N BOND ORTHO TO AN AROMATIC C-O BOND

A method for producing an arene with an aromatic C—N bond ortho to an aromatic C—O bond from a hydroxy arene comprising said aromatic C—O bond is provided. This method comprising the steps a) ortho-oxygenating the hydroxy arene to produce an ortho-quinone, b) condensating the ortho-quinone with a nitrogen nucleophile to generate a compound of Formula (IVa) or (IVb), and c) allowing 1,5-hydrogen atom shift of the compound of Formula (IVa) or (IVb), thereby producing arenes with a C—N bond ortho to a C—O bond of Formula (Va) and (Vb), respectively: 2. The method of claim 1 , wherein the nitrogen nucleophile is of Formula (IIIa) and wherein R claim 1 , R claim 1 , and Reach independently represent:a hydrogen atom, aryl unsubstituted or substituted with one or more hydroxy,', 'hydroxy,', 'alkoxy unsubstituted or substituted with one or more aryl,', 'aminoalkyl or aminodialkyl,', 'alkoxy carbonyl,', 'alkylthio,', 'heterocycloalkyl, and', 'halogen atom,, 'alkyl unsubstituted or substituted with one or more one or more substituents selected from the group consisting ofcycloalkyl,alkenyl,hydroxyl,{'sup': 20', '20, '—C(═O)—O—R), wherein Ris aliphatic or aromatic (preferably alkyl, aryl or an amino acid) unsubstituted or substituted, or'} alkyl unsubstituted or substituted with one or more halogen atoms,', 'alkoxy,', 'aryl unsubstituted or substituted with one or more alkyl, the alkyl being unsubstituted or substituted with one or more halogen atoms,', 'nitro,', 'sulfonamine, and', 'halogen atom; or, 'aryl or heteroaryl unsubstituted or substituted with one or more one or more substituents selected from the group consisting of{'sup': 1', '3, 'Rand Rtogether with the carbon atom to which they are attached form a ring; or'}{'sup': 1', '2, 'Rand Rtogether with the carbon and nitrogen atoms to which they are attached form a ring, thatis saturated or unsaturated;is unsubstituted or substituted with one or more hydroxy;{'sup': '2', 'optionally comprises, in addition to the nitrogen ...

METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS

The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides. 2. The method of claim 1 , wherein R is a methyl group.3. A method for synthesizing N-palmitoyl-D-erythro-sphingosine claim 1 , comprising the steps of:a) allowing (1R,2R,5R)-(+)-2-hydroxy-3-pinanone to react with ethylglycinate under conditions effective to yield (1R,2R,5R)-ethyl-((2-hydroxypinan-3-ylene)amino)acetate;b) allowing (1R,2R,5R)-ethyl-((2-hydroxypinan-3-ylene)amino)acetate (Compound IIIb) to react with 2-(E)-hexadecen-1-al in the presence of chlorotitanium triisopropoxyde and triethylamine under conditions effective to yield one or both of (2S,3R,E)-ethyl 3-hydroxy-2-((E)-((1S,2S,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-ylidene)amino)octadec-4-enoate and (2S,3R,E)-isopropyl 3-hydroxy-2-((E)-((1S,2S,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-ylidene)amino)octadec-4-enoate;c) allowing the one or both of (2S,3R,E)-ethyl 3-hydroxy-2-((E)-((1S,2S,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-ylidene)amino)octadec-4-enoate and (2S,3R,E)-isopropyl 3-hydroxy-2-((E)-((1S,2S,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-ylidene)amino)octadec-4-enoate to react with hydrochloric acid under conditions effective to yield one or both of (2R,3R,E)-ethyl 2-amino-3-hydroxyoctadec-4-enoate and (2R,3R,E)-propyl 2-amino-3-hydroxyoctadec-4-enoate;d) allowing the one or both of (2R,3R,E)-ethyl 2-amino-3-hydroxyoctadec-4-enoate and (2R,3R,E)-propyl 2-amino-3-hydroxyoctadec-4-enoate to react with sodium borohydride under conditions effective to yield D-erythro-sphingosine; ande) allowing D-erythro-sphingosine to react with palmitic acid under conditions effective to yield N-palmitoyl-D-erythro-sphingosine.4. A method for synthesizing an N-acyl-D- ...

A PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY PURE NOREPINEPHRINE

The invention concerns a new, efficient process for the preparation of enantiomerically pure norepinephrine (also known as noradrenaline), or an addition salt thereof, using a catalytic hydrogenation system under hydrogen donor transfer. The invention also discloses a novel intermediate and the process for the preparation thereof. 2. The process of wherein in the compound of formula III R is selected from the group of hydrogen claim 1 , a carboxyl group claim 1 , an alkyl radical having from of 1 to 17 carbon atoms claim 1 , or an aryl radical of not more than 12 carbon atoms claim 1 , said alkyl claim 1 , cycloalkyl and aryl radical being optionally substituted by a further carboxyl group.3. The process of wherein in step a) in the compound of formula IV X is Cl claim 1 , the solvent is water and the auxiliary base is triethylamine or benzylamine.4. The process of wherein in step a) the carboxylic acid is selected from the group consisting of formic claim 1 , acetic claim 1 , propionic claim 1 , oxalic claim 1 , malonic claim 1 , succinic claim 1 , benzoic claim 1 , toluic claim 1 , o-phthalic and tartaric acid claim 1 , preferably formic acid and acetic acid.5. The process of claim 1 , wherein step b) comprises reacting a compound of Formula III with hydrogen or an hydrogen source in the presence of a suitable catalyst claim 1 , to obtain enantioselectively a compound of Formula V and optionally isolating the compound of Formula V as a free base or acid addition salt thereof.7. The process of claim 6 , wherein in the compounds of formula VI n is 1 and the catalyst is selected from the group of C3-[(S claim 6 ,S)-teth-TsDPEN-RuCl] claim 6 , C3-[(S claim 6 ,S)-teth-MtsDPEN-RuCl] claim 6 , C3-[(S claim 6 ,S)-teth-MesDPEN-RuCl] claim 6 , and C3-[(S claim 6 ,S)-teth-TrisDPEN-RuCl] claim 6 , preferably C3-[(S claim 6 , S)-teth-TsDPEN-RuCl].8. The process of wherein step c) comprises reacting compound of Formula V with hydrogen or a hydrogen source claim 1 , in the ...

CLOMIPHENE SYNTHESIS USING A SINGLE SOLVENT

The present invention provides a one-pot method for synthesizing clomiphene (a mixture of the isomers cis-clomiphene and trans-clomiphene) utilizing a single solvent. In a preferred embodiment, the single solvent is dichloromethane (DCM, also known as methylene chloride). The present invention provides an improved method for synthesizing clomiphene and purifying clomiphene isomers. 2. The method of claim 1 , wherein the solvent is dichloromethane.3. The method of wherein the mineral acid in step (a) is sulfuric acid.4. The method of claim 1 , wherein the chlorinating agent in step (b) is N-chlorosuccinimide.5. The method of claim 3 , wherein the solution is maintained at a temperature of about 0° C. during addition of the mineral acid in step (a).6. The method of wherein a suitable base is added to the clomiphene solution obtained in step (b) thereby converting clomiphene to the free base form.7. The method of claim 6 , wherein saturated aqueous sodium bicarbonate solution is added to the clomiphene solution obtained in step (b).8. The method of claim 6 , comprising loading the solution comprising clomiphene free base onto a chromatographic column and eluting the column under conditions suitable for obtaining essentially pure trans-clomiphene.9. The method of further comprising recrystallizing the trans-clomiphene.10. A method for preparing essentially pure trans-clomiphene isomer comprising dissolving a desired quantity of 1-{4-[2-(Diethylamino)ethoxy]phenyl}-1 claim 8 ,2-diphenylethanol in a suitable amount of dichloromethane and thereafter(a) adding to the dichloromethane solution a mineral acid in an amount effective to dehydrate the 1-{4-[2-(Diethylamino)ethoxy]phenyl}-1,2-diphenylethanol thereby producing a 2-{4-[(Z)-1,2-diphenylvinyl]phenoxy}-N,N-di ethyl ethanaminium salt; and thereafter(b) adding to the dichloromethane solution N-chlorosuccinimide in an amount effective to chlorinate the 2-{4-[(Z)-1,2-diphenylvinyl]phenoxy}-N,N-diethyl ethanaminium salt ...

Method for Preparing Levobunolol Hydrochloride

The present invention provides a method for preparing levobunolol hydrochloride. In the present invention S-1-tert-butyl-epoxy methylamine is subjected to a substitution reaction with 5-hydroxy-1-tetralone, and acidified to obtain the target product levobunolol hydrochloride. The method provided by the present invention greatly improves the regioselectivity of the reaction, avoids the occurrence of side reactions, and effectively improves the yield and optical purity of levobunolol hydrochloride, with the yield being 87.3%, and the ee value being over 99%. 1. A method for preparing levobunolol hydrochloride , comprising the following steps:mixing 5-hydroxy-1-tetralone with S-1-tert-butyl-epoxymethylamine, an alkaline agent and a solvent, to obtain S-5-(3′-tert-butylamino-2′-hydroxy)-propoxy-3,4-dihydro-1(2H)tetralone through a substitution reaction; andacidifying S-5-(3′-tert-butylamino-2′-hydroxy)-propoxy-3,4-dihydro-1(2H)tetralone to give levobunolol hydrochloride;wherein the method for preparing 5-hydroxy-1-tetralone comprises the following steps:mixing 1,5-dihydroxynaphthalene, a metal catalyst, a reducing agent and an alcohol-water solven to obtain 5-hydroxy-1-tetralone through a reduction reaction;wherein the reducing agent comprises one or more of ammonium formate, sodium formate, potassium formate, formic acid and hydrazine hydrate: and the molar ratio of the reducing agent to 1,5-dihydroxynaphthalene is (1-3):1.2. (canceled)3. The preparation method of claim 2 , wherein the metal catalyst comprises palladium on carbon or raney nickel; and the mass of the metal catalyst is 0.5% to 10% by mass of 1 claim 2 ,5-dihydroxynaphthalene.4. (canceled)5. The preparation method of claim 2 , wherein the alcohol compound in the alcohol-water solvent comprises one or more of methanol claim 2 , ethanol claim 2 , n-propanol claim 2 , isopropanol claim 2 , n-butanol claim 2 , isobutanol and sec-butanol; the mass ratio of the alcohol compound to water in the alcohol-water ...

Process for manufacturing hydroxyethyl ethylene amines

A process for preparing hydroxyethyl ethylene amines and/or ethylene urea derivatives thereof includes reacting monoethylene glycol with an amine-functional compound having at least two —NH— units, of which at least one is selected from the group of primary amine groups and cyclic secondary amine groups, in the presence of a carbon oxide-delivering agent. The amine-functional compound includes at least one —NH—CH2-CH2-NH— unit, wherein one or more —NH—CH2-CH2-NH— units in the amine-functional compound may be present in the form of piperazine moieties or ethylene urea moieties. The molar ratio of amine-functional compound to monoethylene glycol is in the range of 0.2:1 to 1.5:1 and the molar ratio of carbon oxide-delivering agent to —NH—CH2-CH2-NH— units in the amine-functional compound is at least 0.5:1. The process allows the conversion of monoethylene glycol into ethanol amines in the absence of metals-containing catalysts and without using ammonia.

PROCESS FOR THE PREPARATION OF OPTICALLY PURE FESOTERODINE DERIVATIVES

3,3-diphenylpropylamines of general formula (I), particularly Fesoterodine, as well as their enantiomers, solvates and salts, can be produced by treating a compound of formula (II) with a chiral alcohol to yield the diastereomeric esters of formula (IV) and (IV′), which can be further transformed into a compound of formula (I), or an enantiomer, solvate or salt thereof, wherein R1 is C1-C8 alkyl; and R2 and R3, independently of one another, represent H or C1-C6 alkyl, or together form a ring of 3 to 7 members with the nitrogen to which they are bound. 2. The process according to claim 1 , wherein the chiral alcohol of formula (III) is a chiral secondary alcohol wherein the hydroxyl group is attached directly to a chiral centre.3. The process according to claim 2 , wherein the chiral alcohol of formula (III) is selected from (D)-(+)-menthol claim 2 , (L)-(−)-menthol and (S)-1-phenylethanol.4. The process according to claim 3 , wherein the chiral alcohol of formula (III) is selected from (D)-(+)-menthol and (L)-(−)-menthol.5. The process according to claim 1 , wherein Rand Rare independently selected from C-Calkyl.6. The process according to claim 4 , wherein R claim 4 , Rand Rare isopropyl.7. The process according to claim 1 , wherein Ris hydrogen.8. The process according to claim 1 , wherein Ris selected from —C(O)Cl and —C(O)Br.10. The process according to claim 1 , wherein the compound of formula (I) or (I′) in the free amine form is further converted into a salt thereof by treatment with an acid.11. The process according to claim 1 , wherein the compound of formula (I) or a salt or solvate thereof is selected from the group consisting of Fesoterodine claim 1 , Fesoterodine fumarate claim 1 , Fesoterodine hydrochloride claim 1 , and a solvate thereof.14. The process according to claim 12 , wherein Fesoterodine in the free amine form is further converted into a salt thereof.15. The process according to claim 14 , wherein Fesoterodine is further converted into ...

Cyclic Process for Producing Taurine from Monoethanolamine

There is disclosed a cyclic process for producing taurine from monoethanolamine comprising the steps of: (a) recovering monoethanolamine sulfate from an aqueous mother liquor solution; (b) reacting the monoethanolamine sulfate with sulfuric acid to form an aqueous solution comprised of monoethanolamine bisulfate; (c) heating the aqueous solution comprised of the monoethanolamine sulfate and optionally added monoethanolamine sulfate to yield 2-aminoethyl hydrogen sulfate ester; and (d) reacting the ester with ammonium sulfite or an alkali sulfite to yield taurine.

PROCESS OF MANUFACTURING AN ELECTRON TRANSPORT MATERIAL

A process of dissolving [6,6]-phenyl-C-butyric-N-2-dimethylaminoethyl ester in a solvent to produce a first mixture. A reagent is added to the first mixture to produce a second mixture. The second mixture is then refluxed to produce [6,6]-phenyl-C-butyric-N-2-trimethylammonium ethyl ester iodide. 1. A process comprising:{'sub': '60', 'a) dissolving [6,6]-phenyl-C-butyric-N-2-dimethylaminoethyl ester in a solvent to produce a first mixture;'}b) adding a reagent to the first mixture to produce a second mixture;{'sub': '60', 'c) heating the second mixture to produce [6,6]-phenyl-C-butyric-N-2-trimethylammonium ethyl ester iodide.'}2. The process of claim 1 , wherein [6 claim 1 ,6]-phenyl-C-butyric-N-2-dimethylaminoethyl ester is produced from:{'sub': '60', 'a) dissolving [6,6]-phenyl-C-butyric acid methyl ester in 1,2-dichlorobenzene, under an oxygen free environment, to produce a first mixture;'}b) adding dibutyltin(IV) oxide to the first mixture to produce a second mixture;c) adding 2-(dimethylamino)ethan-1-ol to the second mixture to produce a third mixture; and{'sub': '60', 'd) refluxing the third mixture to produce [6,6]-phenyl-C-butyric-N-2-dimethylaminoethyl ester.'}3. The process of claim 1 , wherein the solvent is an organic solvent.4. The process of claim 1 , wherein the solvent is selected from the group consisting of: dichlorobenzene claim 1 , chlorobenzene claim 1 , xylene claim 1 , toluene claim 1 , chloroform claim 1 , tetrahydronaphthalene claim 1 , carbon disulfide claim 1 , dichloromethane claim 1 , ethyl acetate claim 1 , chloroform claim 1 , ethanol claim 1 , hexane claim 1 , cyclohexane claim 1 , tetrahydrofuran and isopropanol.5. The process of claim 1 , wherein the reagent is halomethanes claim 1 , iodomethane claim 1 , any aliphatic iodide claim 1 , dimethyl sulfate claim 1 , methyl triflate claim 1 , or dimethyl carbonate.6. The process of claim 1 , wherein the second mixture is heated to a temperature of at least 50° C.7. The process of claim ...

SALTS OF OBETICHOLIC ACID

The invention relates to salts of Obeticholic Acid, their amorphous and crystalline polymorphic form and processes for preparation thereof. 1. L-arginine salt of Obeticholic Acid.2. A process for preparing L-arginine salt of Obeticholic Acid of claim 1 , comprising the steps of:(a) providing Obeticholic Acid and L-Arginine in water and a water miscible solvent to obtain a reaction mixture,(b) heating the reaction mixture,(c) removing the solvent, and(d) isolating the L-arginine salt of Obeticholic Acid.3. The process according to wherein the water miscible solvent is selected from the group comprising of methanol claim 2 , ethanol claim 2 , tetrahydrofuran claim 2 , acetone and acetonitrile.4. L-lysine salt of Obeticholic Acid.5. A process for preparing L-lysine salt of Obeticholic Acid of claim 4 , comprising the steps of:(a) providing Obeticholic Acid and L-lysine in water and a water miscible solvent to obtain a reaction mixture,(b) heating the reaction mixture,(c) removing the solvent, and(d) isolating the L-arginine salt of Obeticholic Acid.6. The process according to wherein the water miscible solvent is selected from the group comprising of methanol claim 5 , ethanol claim 5 , tetrahydrofuran claim 5 , acetone and acetonitrile.7. Ammonium salt of Obeticholic Acid.8. A process for preparing the ammonium salt of Obeticholic Acid of comprising the steps of:(a) providing Obeticholic Acid in a water miscible solvent and aqueous ammonia,(b) removing the solvent, and(c) isolating the ammonium salt of Obeticholic Acid.9. The process according to wherein the water miscible solvent is selected from the group comprising of methanol claim 8 , ethanol claim 8 , tetrahydrofuran claim 8 , acetone and acetonitrile.10. Tris (hydroxymethyl) aminomethane salt of Obeticholic Acid.11. A process for preparing the Tris (hydroxymethyl) aminomethane salt of Obeticholic Acid of claim 10 , comprising the steps of:(a) providing Obeticholic Acid and Tris(hydroxymethyl)aminomethane buffer ...

Nickel Containing Hydrosilylation Catalysts and Compositions Containing the Catalysts

A composition contains (A) a hydrosilylation reaction catalyst and (B) an aliphatically unsaturated compound having an average, per molecule, of one or more aliphatically unsaturated organic groups capable of undergoing hydrosilylation reaction. The composition is capable of reacting via hydrosilylation reaction to form a reaction product, such as a silane, a gum, a gel, a rubber, or a resin. Ingredient (A) contains a metal-ligand complex that can be prepared by a method including reacting a metal precursor and a ligand, 2. (canceled)4. The method of claim 1 , further comprising (2) combining an ionic activator with the reaction product.6. The method of claim 5 , where at least one of the following conditions is satisfied:Condition (I) is met and the ligand has general formula (ii), and the ligand is selected from the group consisting of ligands 510, 8838, 8856, and 8945 in Table 2; orCondition (I) is met and the ligand has general formula (iii), and the ligand is selected from the group consisting of ligands 10364 in Table 2; orCondition (I) is met and the ligand has general formula (iv), and the ligand is selected from the group consisting of ligands 3746, 10132, and 10218 in Table 2; orCondition (I) is met and the ligand has general formula (vi), and the ligand is selected from the group consisting of ligands 2272 in Table 2; orCondition (I) is met and the ligand has general formula (vii), and the ligand is selected from the group consisting of ligands 1936, 2956 and 6417 in Table 2; orCondition (I) is met and the ligand has general formula (viii), and the ligand is selected from the group consisting of ligands 3746 in Table 2; orCondition (I) is met and the ligand has general formula (xii), and the ligand is selected from the group consisting of ligands 10394 in Table 2; orCondition (I) is met and the ligand has general formula (xiii), and the ligand is selected from the group consisting of ligands 10405 in Table 2; orCondition (II) is met and the ligand has ...

AN IMPROVED PROCESS FOR THE PREPARATION OF 3-ARYLOXY-3-PHENYLPROPYLAMINE AND SALT THEREOF

The present invention relates to an industrially feasible and economically viable process for the preparation of 3-aryloxy-3-phenylpropylarnine and salt of formula I thereof. 2. The process according to claim 1 , whereinin step a), high boiling point polar aprotic solvent is selected from dimethyl sulphoxide or dimethylformamide or mixtures thereof:in step a), e) or h), inorganic base is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate or lithium bicarbonate,in step b), e), h), or i), hydrocarbon solvent is selected from toluene or xylene or mixtures thereof;in step f), ester solvent is selected from ethyl acetate, isopropyl acetate or methyl acetate or mixtures thereof:in step j), ether solvent is selected from diethyl ether or diisopropyl ether or mixtures thereof and nitrile solvent is selected from acetonitrile or propionitrile or mixtures thereof; andin step l), suitable solvent is selected from alcohols include methanol, ethanol, n-propanol or isopropanol, hydrocarbons include toluene or xylene, nitriles include acetonitrile or propionitrile and/or mixtures thereof.3. A process for preparing pure atomoxetine hydrochloride having HPLC purity more than 99.5% and chiral HPLC ratio R/S>99.9/0.1 obtained from (S)-(+)-mandelic acid salt of (R)-tomoxetine formula IV having HPLC purity 97±1% and Chiral HPLC ratio R/S 90/10±3.4. The process according to claim 3 , wherein (S)-(+)-mandelic acid salt of (R)-tomoxetine formula IV converted to atomoxetine free base residue by treating with base.5. The process according to claim 4 , wherein atomoxetine free base residue is treated with IPA-HCl in solvent combination of ether and nitrile to form atomoxetine hydrochloride.6. The process according to claim 5 , wherein atomoxetine hydrochloride optionally be purified with suitable solvent.7. A process for the preparation of compound of formula III comprising ...

An improved process for the preparation of Dolutegravir

The present invention provides (R)-3-Amino-1-butanol (D)-tartarate (IIb); process for its preparation and its conversion to Dolutegravir. The present invention also provides an improved process for the preparation of Dolutegravir (I) or pharmaceutically acceptable salts wherein compound (XVI) is reacted with an optically active acid addition salt of (R)-3-amino-1-butanol (IIa). 2. (canceled)4. The process according to claim 3 , wherein the reaction is carried out in presence of a solvent comprising a hydrocarbon claim 3 , an ether claim 3 , an alcohol or mixtures thereof.5. (canceled)6. (canceled)8. The process according to claim 7 , wherein the hydrogenation claim 7 , in step-(i) is carried out in the presence of hydrogenation catalyst in a solvent selected from the group comprising methanol claim 7 , ethanol claim 7 , isopropanol claim 7 , n-propanol claim 7 , n-butanol claim 7 , formic acid claim 7 , acetic acid claim 7 , water or the mixture thereof.9. The process according to claim 8 , wherein the hydrogenation catalyst is selected form the group comprising palladium in the form of Pd—C claim 8 , Pd(OH)/C;platinum in the form of PtO claim 8 , and nickel in the form of Ra—Ni claim 8 , Urushibara nickel claim 8 , rhodium complex claim 8 , ruthenium complex.10. (canceled)11. The process according to claim 7 , wherein the optically active acid is selected form the group comprising tartaric acid claim 7 , dibenzoyltartaric acid claim 7 , mandelic acid claim 7 , camphoric acid claim 7 , camphorsulfonic acid claim 7 , p-hydroxymandelic acid claim 7 , p-Cl-mandelic acid claim 7 , phenoxypropionic acid claim 7 , p-hydroxyphenoxypropionic acid or lactic acid or mixture thereof.12. The process according to claim 7 , wherein the diastereomeric salt of (R)-3-amino-1-butanol with an optically active acid (IIa) is treated with a base selected from the group comprising alkali or alkaline earth metal hydroxide claim 7 , alkali metal carbonate claim 7 , alkali metal ...

METHOD FOR PREPARATION OF ARYL POLY(OXALKYL) QUATERNARY AMMONIUM COMPOUND

A method for preparation of an aryl poly(oxalkyl) quaternary ammonium compound is provided, said method comprising steps of: 1) reacting a phenol with a dihalopolyalkylene ether under the action of a phase transfer catalyst, to obtain an arylpoly(oxalkyl) halide; 2) reacting said arylpoly(oxalkyl) halide with an amination reagent under the action of a phase transfer catalyst, to obtain an arylpoly(oxalkyl) amine; 3) reacting said arylpoly(oxalkyl) amine with an alkylation reagent, to obtain an aryl poly(oxalkyl) quaternary ammonium compound; wherein Ris H or a Cto Calkyl group, located in the ortho, meta or para position; n is an integer of 2 to 6; Ris H or a Cto Calkyl group; Ris H or a Cto Calkyl group; Ris a Cto Calkyl group; Xis Br or Cl; X is Cl, Br, or I. The preparation method according to the present invention requires low temperature and low pressure, the reaction time is short, and an overall yield can reach 75%. The operation is simple, the cost is low, and the product can be separated easily and have a purity of pharmaceutical grade, thereby facilitating the large-scale production. 2. The method according to claim 1 , wherein Ris a Cto Calkyl group claim 1 , Ris a Cto Calkyl group claim 1 , Ris a C˜Calkyl group.3. The method according to or claim 1 , wherein said phenol is one of phenol claim 1 , cresol claim 1 , 5-methyl-2-isopropyl phenol claim 1 , 2-methyl-5-isopropyl phenol claim 1 , p-tert-butyl phenol claim 1 , p-sec-butyl phenol claim 1 , p-tert-pentyl cresol claim 1 , p-sec-octyl phenol or p-tert-octyl phenol; and said dihalopolyalkylene ether is one of β claim 1 ,β′-dichloro diethyl ether claim 1 , β claim 1 ,β′-dichloro diisopropyl ether claim 1 , β claim 1 ,β′-dichloro dibutyl ether claim 1 , β claim 1 ,β′-dichloro dipentyl ether claim 1 , β claim 1 ,β′-dibromo diethyl ether claim 1 , β claim 1 ,β′-dibromo diisopropyl ether claim 1 , β claim 1 ,β′-dibromo dibutyl ether claim 1 , β claim 1 ,β′-dibromo dipentyl ether.4. The method according to ...

METHODS FOR PRODUCING TERTIARY AMINE CATALYSTS AND USES OF SUCH

Method for producing a tertiary amine catalyst comprising reacting a first tertiary amine having two or three hydroxyl moieties and a second tertiary amine having a halogen moiety. Also a method for producing tertiary amine catalysts comprising reacting a tertiary amine having at least two halogen moieties and either (i) a tertiary amine having at least one hydroxyl moiety, or (ii) a heterocyclic compound comprising an amine and an ether functional group. 119-. (canceled)21. The method of claim 20 , wherein Ris a methyl group and each of x and y is 2.23. The method of claim 20 , wherein Ris a hydroxyethyl group and each of x and y is 2.25. The method of claim 20 , wherein the first tertiary amine and second tertiary amine are reacted at a temperature in a range of from about 0 to about 150° C. at a pressure ranging from about 1 atm to about 10 atm.26. The method of claim 25 , wherein the ratio of the first tertiary amine to the second tertiary amine is in a range of from 1:2 to 1:10.27. The method of claim 20 , wherein the first tertiary amine and the second tertiary amine are reacted in the presence of a base.28. A method for producing a tertiary amine catalyst comprising reacting a tertiary amine having at least two halogen moieties and a tertiary amine having at least one hydroxyl moiety.29. The method of wherein the tertiary amine having at least two halogen moieties comprises 2-dimethylamino ethyl chloride or a solution thereof.30. The method of claim 29 , further comprising a step whereby the dimethylamino ethyl chloride is formed by reacting methyl diethanol amine and thionyl chloride.32. The method of claim 28 , wherein the tertiary amine having at least two halogen moieties and a tertiary amine having at least one hydroxyl moiety are reacted in the presence of a base.33. The method of claim 28 , wherein the ratio of the tertiary amine having at least two halogen moieties and the tertiary amine having at least one hydroxyl moiety is in a range of from 1:2 to ...

PROCESS FOR THE PREPARATION OF TAPENTADOL AND ANALOGS THEREOF

The present invention relates to a process for the preparation of tapentadol and analogs or compounds or stereoisomers of formula (I), Formula I wherein, A is aryl, heteroaryl, and cycloalkyl; R is H, OH, OR, halogen, C-Calkyl, cycloalkyl, aryl or heteroaryl; Ris C-Calkyl, cycloalkyl, aryl or heteroaryl, wherein each of these groups may further be substituted with one or more substituent selected from H, OH, halogen, CN, NO, C-Calkyl or phenyl. Further, the multi-step process involves no column chromatography purification until the very last step. This makes this process highly commercially viable and industrially useful. 2. The process according to claim 1 , wherein the acid is selected from a group consisting of trifluoroacetic acid claim 1 , camphor sulphonic acid claim 1 , acetic acid claim 1 , formic acid and hydrochloric acid.3. The process according to claim 1 , wherein the reducing agent is sodium borohydride or lithium aluminum hydride.4. The process according to claim 1 , wherein the organic solvent is selected from dichloromethane claim 1 , tetrahydrofuran claim 1 , dimethylsulfoxide claim 1 , dimethyformamide claim 1 , dioxin claim 1 , acetonitrile claim 1 , ethylacetate claim 1 , hexane claim 1 , pentane claim 1 , toluene claim 1 , acetone and diethylether.5. The process according to claim 1 , wherein the transition metal containing reducing agent is Raney Ni.6. The process according to claim 1 , wherein the halide is selected from group consisting of bromide and chloride.7. The process according to claim 1 , wherein the alcoholic solvent is selected from a group consisting of ethanol claim 1 , methanol claim 1 , propanol and butanol.8. The process according to claim 1 , wherein the mineral acid is selected from a group consisting of hydrochloric acid claim 1 , sulphuric acid claim 1 , and hydrobromic acid.9. The process according to claim 1 , wherein all of process steps are purification-free steps.10. The process according to claim 1 , wherein the ...

REACTION OF GLYCOLADEHYDE

A two-step one-pot process for reacting glycolaldehyde with an aminating agent in the presence of a reactive organic fluid for instance a reactive solvent is provided. The first step comprises of contacting glycolaldehyde with an aminating agent in the presence of a reactive fluid for instance a reactive solvent under inert atmosphere to produce unsaturated intermediates, and reacting the reaction mixture obtained in step 1 with hydrogen in the presence of a supported hydrogenation catalyst in a second step. 1. A process for preparing alkanolamines and diamines , characterized by a two-step procedure wherein step 1 comprises under inert atmosphere and in a reactive organic fluid reacting of glycolaldehyde with an aminating agent , whereof at least part of molecules of the organic fluid contain a labile H+ or have an acidic , eventually weak acidic hydrogen , to give unsaturated intermediates and step 2 comprises hydrogenating the reaction mixture obtained in the first step under a hydrogen atmosphere whilst in contact with a supported hydrogenation catalyst and still in the reactive organic fluid.2. (canceled)3. The process according to claim 1 , whereby the organic fluid comprises molecules that have an hydrogen atom bound to an oxygen (as in a hydroxyl group) or bound to an nitrogen (as in an amine group) so that the organic fluid readily participates in the formation of unsaturated intermediates by donating protons (H+).46-. (canceled)7. The process according to claim 1 , wherein the reaction is conducted in a two-step one-pot procedure.8. The process according to claim 1 , whereby the first step comprises reacting the glycolaldehyde with an aminating agent of the groups consisting of ammonia (NH) claim 1 , at least one primary amine (NHR) and at least one secondary amine (NHR′R″) and in contact with claim 1 , solved in or in the presence of the organic fluid to give unsaturated intermediates.9. The process according to claim 8 , whereby the aminating agent is ...

SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

Provided are immediate or prolonged administration of certain salts of Kchannel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving Kchannels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals. 1129-. (canceled)130. A method for activating Kchannels in an obese , overweight , or obesity prone subject , comprising administering to the subject a therapeutically effective amount of polymorph B of diazoxide choline in combination with a melanocortin-4-receptor agonist.131. The method of wherein the polymorph B of diazoxide choline has characteristic peaks in the XRPD pattern at values of two-theta (Cu Kα claim 130 , 40 kV claim 130 , 40 mA) at approximately 8.9 claim 130 , 10.3 claim 130 , 12.0 claim 130 , 18.3 claim 130 , 20.6 claim 130 , 24.1 claim 130 , 24.5 claim 130 , 26.3 claim 130 , 27.1 claim 130 , and 28.9 degrees.132. The method of wherein the polymorph B of diazoxide choline has characteristic infrared absorbances at 3256 claim 130 , 2174 claim 130 , 2890 claim 130 , 1605 claim 130 , 1463 claim 130 , and 1235 cm.133. The method of wherein the polymorph B of diazoxide choline has characteristic peaks in the XRPD pattern substantially as shown in and an NMR spectrum substantially as shown in .134. The method of wherein between 10 and 100 mg of the polymorph B of diazoxide choline is administered per dose.135. The method of wherein between 100 and 200 mg of the polymorph B of diazoxide choline is administered per dose.136. The method of wherein between 200 and 300 mg of the polymorph B of diazoxide choline is administered per dose.137. The method of ...

Polybrominated diphenyl-based flame retardant compounds

A process of forming a flame retardant material is disclosed. The process includes forming a functionalized polybrominated diphenyl-based flame retardant compound having the following structural formula: In the structural formula, X corresponds to a functional group. The process also includes forming a flame retardant material by covalently bonding the functionalized polybrominated diphenyl-based flame retardant compound into a material using the functional group.

Iridium Containing Hydrosilylation Catalysts and Compositions Containing the Catalysts

A composition contains (A) a hydrosilylation reaction catalyst and (B) an aliphatically unsaturated compound having an average, per molecule, of one or more aliphatically unsaturated organic groups capable, of undergoing hydrosilylation reaction. The composition is capable of reacting via hydrosilylation reaction to form a reaction product, such as a silane, a gum, a gel, a rubber, or a resin. Ingredient (A) contains a metal-ligand complex that can be prepared by a method including reacting a metal precursor and a ligand.

Use of nitrogen compounds quaternised with alkylene oxide and hydrocarbyl-substituted polycarboxylic acid as additives in fuels and lubricants

The invention relates to the use of quaternized nitrogen compounds as a fuel and lubricant additive or kerosene additive, such as in particular as a detergent additive, for decreasing or preventing deposits in the injection systems of direct-injection diesel engines, in particular in common rail injection systems, for decreasing the fuel consumption of direct-injection diesel engines, in particular of diesel engines having common rail injection systems, and for minimizing the power loss in direct-injection diesel engines, in particular in diesel engines having common rail injection systems; the invention further relates to the use as an additive for petrol, in particular for operation of DISI engines.

A PROCESS FOR THE PREPARATION OF VERAPAMIL HYDROCHLORIDE

A process for the preparation of 5-(3,4-dimethoxyphenylethyl) methyl-amino-2-(3,4-dimethoxyphenyl)-2-isopropyl valeronitrile, which is known as Verapamil is described. A process for improving the purity of verapamil and therefore of its hydrochloride represented as the compound of formula I, by efficient removal of the impurities formed, affording a product of purity greater than 99% is described. 2. The process according to claim 1 , wherein the quaternary ammonium salt phase transfer catalyst used in step (a) is selected from the group consisting of tricaprylyl methyl ammonium chloride (Aliquat 336) claim 1 , tetra-n-butylammonium bromide claim 1 , benzyltriethylammonium chloride (TEBA) claim 1 , cetyltrimethylammonium bromide claim 1 , cetylpyridinium bromide claim 1 , N-benzylquininium chloride claim 1 , tetra-n-butylammonium chloride claim 1 , tetrabutylammonium bromide (TBAB) claim 1 , tetra-n-butylammonium hydroxide claim 1 , tetra-n-butylammonium iodide claim 1 , tetraethylammonium chloride claim 1 , benzyltributylammonium chloride claim 1 , hexadecyltrimethylammonium chloride claim 1 , tetramethylammonium chloride claim 1 , hexadecyltrimethylammonium chloride claim 1 , and octyltrimethylammonium chloride or combinations thereof.3. The process according to claim 1 , wherein the phase transfer catalyst used in step (a) of is tetrabutylammonium bromide.4. The process according to claim 1 , wherein the base used in step (a) is an inorganic base selected from the group consisting of sodium hydroxide claim 1 , potassium hydroxide claim 1 , lithium hydroxide claim 1 , cesium hydroxide claim 1 , magnesium hydroxide claim 1 , calcium hydroxide claim 1 , sodium carbonate claim 1 , potassium carbonate claim 1 , cesium carbonate claim 1 , sodium bicarbonate and potassium bicarbonate; or combinations thereof in a solvent.5. The process according to claim 1 , wherein the base used in step (a) of is sodium hydroxide in water as solvent.6. The process according to claim 1 ...

Ionomeric cross-linkers and membranes formed therefrom

The present invention is the use of a compound comprising two or more covalently bonded polymerisable vinyl groups and one or more covalently bonded ionic groups selected from a quaternary ammonium group; a quaternary phosphonium group; or a tertiary sulphonium group, as an ionic cross-linker. The cross-linkers of the invention may be used to form an ionomer membrane. Methods for forming the cross-linkers of the invention are also disclosed.

FLUORENE DERIVATIVE AND USE THEREOF

Provided is the fluorene derivative represented in formula (1). 2. The fluorene derivative of claim 1 , wherein Rand Rare both an alkyl group of 2 to 20 carbon atoms which includes at least one ether structure.3. The fluorene derivative of or claim 1 , wherein nand nare both 0.4. A charge-transporting substance consisting of the fluorene derivative of .5. A charge-transporting varnish comprising the charge-transporting substance of and an organic solvent.6. The charge-transporting varnish of which further comprises a dopant substance.7. A charge-transporting thin-film produced using the charge-transporting varnish of or .8. An organic electroluminescent device comprising the charge-transporting thin-film of . This invention relates to a fluorene derivative and to the use thereof.Charge-transporting thin-films made of organic compounds are used as emissive layers and charge injection layers in organic electroluminescent (EL) devices. In particular, a hole injection layer is responsible for transferring charge between an anode and a hole-transporting layer or an emissive layer, and thus serves an important function in achieving low-voltage driving and high brightness in organic EL devices.Processes for forming the hole injection layer are broadly divided into dry processes such as vapor deposition and wet processes such as spin coating. Comparing these different processes, wet processes are better able to efficiently produce thin-films having a high flatness over a large area. Hence, with the progress being made today toward larger-area organic EL displays, there exists a desire for hole injection layers that can be formed by wet processes.In view of these circumstances, the inventors have developed charge-transporting materials which can be employed in various wet processes and which, when used in hole injection layers for organic EL devices, are capable of achieving excellent EL device characteristics. The inventors have also developed compounds of good solubility ...

N,N-DIMETHYLAMINOETHYL ACRYLATE COMPOSITION STABILIZED IN RESPECT OF DISCOLORING EFFECTS

The invention relates to the use of 2,6,-di-tert-butyl-4-methylphenol at a moiety of 25 to 200 ppm for stabilizing N,N-dimethylaminoethyl acrylate in respect of discoloring effects. The invention also relates to an N,N-dimethylaminoethyl acrylate stabilized in said manner and to a method for producing the same. 1. A composition of N ,N-dimethylaminoethyl acrylate that is stabilized with respect to coloration , comprising from 25 to 200 ppm of 2 ,6-di-tert-butyl-4-methylphenol.2. The composition as claimed in having a coloration of less than 100 Apha.3. The composition as claimed in further comprising at least one polymerization inhibitor claim 1 , selected from the group consisting of hydroquinone claim 1 , hydroquinone methyl ether (MEHQ) and mixtures thereof.4. A process for the continuous production of a composition of N claim 1 ,N-dimethylaminoethyl acrylate that is stabilized with respect to coloration claim 1 , according to claim 1 , said process comprising the steps of transesterifying a light acrylate selected from the group consisting methyl acrylate and ethyl acrylate claim 1 , with dimethylaminoethanol in the presence of a catalyst claim 1 , followed by a treatment for purifying a reaction mixture comprising a final distillation of purified N claim 1 ,N-dimethylaminoethyl acrylate claim 1 , wherein 25 to 200 ppm of 2 claim 1 ,6-di-tert-butyl-4-methylphenol are introduced at an outlet of the distilled gaseous stream of purified N claim 1 ,N-dimethylaminoethyl acrylate claim 1 , before condensation of final product.5. The process of claim 4 , comprising the following steps:a) transesterifying a light acrylate selected from the group consisting methyl acrylate and ethyl acrylate, with dimethylaminoethanol in the presence of a transesterification catalyst and at least one polymerization inhibitor, a corresponding azeotropic mixture of light acrylate/light alcohol being drawn off continuously during the reaction; at the top, a stream composed essentially of N, ...

METHODS AND INTERMEDIATES FOR SYNTHESIZING SK1-I

The invention provides methods for synthesizing the compound (2R,3S,4E)-N-methyl-5-(4′-pentylphenyl)-2-aminopent-4-ene-1,3-diol, also known as SK1-I, and intermediate compounds used in its synthesis. 2. The method of claim 1 , wherein R is a linear alkyl group.3. The method of claim 1 , wherein R is a branched alkyl group.5. The method of claim 4 , wherein R is a linear alkyl group.6. The method of claim 5 , wherein R is a CHgroup.7. The method of claim 4 , wherein R is a branched alkyl group. This application is a continuation of U.S. patent application Ser. No. 16/169,056 filed Oct. 24, 2018, which claims the benefit of U.S. provisional application Ser. No. 62/576,943 filed Oct. 25, 2017 each of which is hereby incorporated by reference in its entirety.The present invention relates to the field of organic synthesis of pharmaceutical compounds.(2R,3S,4E)-N-methyl-5-(4′-pentylphenyl)-2-aminopent-4-ene-1,3-diol, also known as SK1-I and BML-258 (as HCl salt), is a pharmaceutical inhibitor of sphingosine kinase 1 initially described in Paugh et al., Blood. 2008 Aug. 15; 112 (4): 1382-1391. An existing method for synthesizing SK1-I is disclosed in U.S. Pat. No. 8,314,151.What is needed and provided by the present invention are improved methods for synthesizing SK1-I and related compounds.One embodiment of the invention provides a method for synthesizing the compoundthat includes the reaction steps of:Another embodiment of the invention provides a method for synthesizing the compoundthat includes the reaction step of:A further embodiment of the invention provides a method for synthesizingthat includes the steps of: (i) reactingwith DIBAL in the presence of Rochelle salt, thereby obtainingIn one variation of this embodiment, Rochelle salt is provided in an aqueous solution that further includes sodium hydroxide.Still further embodiments of the invention provide complete multi-step syntheses of SK1-I and salts thereof from precursor compounds.The invention also provides ...

PROCESS FOR MANUFACTURING CHAIN-EXTENDED HYDROXYETHYLETHYLENEAMINES, ETHYLENEAMINES, OR MIXTURES THEREOF

The present disclosure pertains to a process for preparing hydroxyethylethyleneamines, ethyleneamines, or mixtures thereof, and/or ethylene urea derivatives thereof. The process includes reacting diethanolamine with an amine-functional compound that includes at least two —NH— units of which at least one is selected from the group of primary amine groups and cyclic secondary amine groups. The amine-functional compound includes at least one —NH—CH2-CH2-NH— unit wherein one or more —NH—CH2-CH2-NH— units in the amine-functional compound may be present in the form of cyclic ethylene urea moieties, piperazine moieties, or linear ethylene urea moieties, in the presence of a carbon oxide delivering agent. 1. A process for preparing hydroxyethylethyleneamines , ethyleneamines , or mixtures thereof , and/or ethylene urea derivatives thereof comprising the step of reacting diethanolamine with an amine-functional compound comprising at least two —NH— units of which at least one is selected from the group of primary amine groups and cyclic secondary amine groups , the amine-functional compound comprising at least one —NH—CH2-CH2-NH— unit wherein one or more —NH—CH2-CH2-NH— units in the amine-functional compound is present in the form of cyclic ethylene urea moieties , piperazine moieties , or linear ethylene urea moieties , in the presence of a carbon oxide delivering agent , whereinthe molar ratio of amine-functional compound to diethanolamine is at least about 0.2:1, andthe molar ratio of carbon oxide delivering agent to —NH—CH2-CH2-NH— units in the amine-functional compound is at least about 0.1:1.2. The process according to claim 1 , wherein the molar ratio of amine-functional compound to diethanolamine is at least about 0.5:1.3. The process according to claim 1 , wherein the molar ratio of the carbon oxide delivering agent to —NH—CH2-CH2-NH— units in the amine-functional compound is from about 0.2:1 to about 3:1.4. The process according to claim 1 , wherein diethanolamine ...

PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY AND NOVEL INTERMEDIATES AND METHODS RELATED THERETO

The present disclosure pertains to peptide nucleic acid (PNA) monomers and oligomers, as well as methods and compositions useful for the preparation of PNA monomer precursors (e.g. PNA Monomer Esters, Backbone Esters and Backbone Ester Acid Salts, as described below) that can be used to prepare PNA monomers wherein said PNA monomers can be used to prepare said PNA oligomers. In some embodiments, the disclosure features sulfonic acid salts of Backbone Ester compounds, which sulfonic acid salts generally tend to be crystalline and can be obtained in reasonably good yield, often without requiring any chromatographic purification of the reaction product of the Backbone Ester synthesis reaction. This disclosure also pertains to novel methods for the synthesis of said Backbone Ester compounds and novel methods for the formation of the related sulfonic acid salts. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethy-(TCE), 2,2,2-tribromoethyl-(TBE), 2-iodoethyl-groups (2-IE) and 2-bromoethyl-(2-BrE) as the ester group. These particular ester groups can be removed under conditions where both Boc and Fmoc protected amine groups are stable. 2. The compound of claim 1 , wherein the sulfonate anion is produced from a sulfonic acid selected from the group consisting of: benzenesulfonic acid claim 1 , naphthalenesulfonic acid claim 1 , p-xylene-2-sulfonic acid claim 1 , 2 claim 1 ,4 claim 1 ,5-trichlorobenzenesulfonic acid claim 1 , 2 claim 1 ,6-dimethylbenzenesulfonic acid claim 1 , 2-mesitylenesulfonic acid claim 1 , 2-mesitylenesulfonic acid dihydrate claim 1 , 2-methylbenzene sulfonic acid claim 1 , 2-ethylbenzenesulfonic acid claim 1 , 2-isopropylbenzenesulfonic acid claim 1 , 2 claim 1 ,3-dimethylbenzenesulfonic acid claim 1 , 2 claim 1 ,4 claim 1 ,6-trimethylbenzenesulfonic acid and 2 claim 1 ,4 claim 1 ,6-triisopropylbenzenesulfonic acid.3. The compound of claim 1 , wherein the sulfonate anion is produced from p-toluenesulfonic acid.4. The compound ...

Process to prepare treprostinil, the active ingredient in remodulin®

This present invention relates to an improved process to prepare prostacyclin derivatives. One embodiment provides for an improved process to convert benzindene triol to treprostinil via salts of treprostinil and to purify treprostinil.

NOVEL INTERMEDIATE FOR SYNTHESIZING TREPROSTINIL DIETHANOLAMINE AND METHOD FOR PREPARING THE SAME

The present invention relates to a method for treprostinil diethanolamine synthesis. The present invention also relates to a novel intermediate used in the method for treprostinil diethanolamine synthesis. The novel intermediate is shown in the following formula (II): 2. The compound as claimed in claim 1 , wherein R1 is a methyl group.3. The compound as claimed in claim 1 , wherein R2 is a methyl group.6. The method as claimed in claim 5 , wherein R2 is a methyl group.8. The method as claimed in claim 7 , wherein R2 is a methyl group.9. The method as claimed in claim 7 , wherein in step (A) claim 7 , the hydroxyl-protecting group is selected from the group consisting of methyl group claim 7 , ethyl group claim 7 , tert-butyl group claim 7 , acetyl group claim 7 , pivaloyl group (Piv) claim 7 , benzyl group (Bn) claim 7 , p-methoxy benzyl group (PMB) claim 7 , 9-fluorenylmethyl group (Fm) claim 7 , diphenylmethyl group (DPM) claim 7 , trimethylsilyl group (TMS) claim 7 , tert-butyldimethylsilyl group (TBS) claim 7 , triisopropylsilyl group (TIPS) claim 7 , 2-methoxylethoxymethyl group (MEM) claim 7 , methylthiomethy group (MTM) claim 7 , methoxymethyl group (MOM) claim 7 , and tetrahydropyranyl group (THP).10. The method as claimed in claim 7 , wherein in step (H) claim 7 , R4 is a methyl group.12. The compound as claimed in claim 11 , wherein R2 is a methyl group. This application claims the benefits of the Taiwan Patent Application Serial Number 103141569, filed on Dec. 1, 2014, the subject matter of which is incorporated herein by reference.1. Field of the InventionThe present invention relates to a method for treprostinil diethanolamine preparation. In addition, the present invention also relates to a novel intermediate for treprostinil diethanolamine preparation.2. Description of Related ArtTreprostinil and derivatives thereof are beneficial for vasodilation stimulation, platelet aggregation and thrombus formation inhibition, thrombolysis stimulation, cell ...

PROCESS FOR THE PREPARATION OF CLOMIPHENE

An improved process for the preparation of the active pharmaceutical ingredient Clomiphene and, in particular, trans-Clomiphene, using acetic acid or trifluoroacetic acid is disclosed. 2. The process according to the claim 1 , wherein the amount of acetic acid or trifluoroacetic acid is between 1 and 3 volumes.3. The process according to claim 1 , wherein the organic solvent is methylene chloride.4. The process according to claim 2 , wherein the amount of methylene chloride is between 5 and 11 volumes.5. The process according to claim 1 , wherein the amount of acetic acid or trifluoroacetic acid is between 1 and 3 volumes and the amount of methylene chloride is between 5 and 11 volumes.6. The process according to the claim 5 , wherein the amount of acetic acid or trifluoroacetic acid is about 2 volumes and the amount of methylene chloride is about 8 volumes.7. The process according to claim 1 , wherein the reacting is performed at a temperature between 20° C. and 40° C.8. The process according to claim 1 , wherein the amount of chlorinating agent is in the range of from 0.45 to 0.60 molecular equivalents.9. The process according to claim 1 , wherein the chlorinating agent is dichlorodimethylhydantoin.10. The process according to claim 1 , wherein the reacting is carried out under anhydrous conditions.12. The process according to claim 11 , wherein the reacting step and the adding of racemic binaphthyl-phosphoric acid are carried out one pot.14. The process according to claim 1 , wherein the Clomiphene prepared by said process is a mixture of trans-Clomiphene and cis-Clomiphene in ratio from 75:25 to 99:1. This application claims the benefit of priority from European Patent Application No. EP 14190736.0, filed Oct. 28, 2014, the disclosure of which is incorporated herein.The present invention refers to a process for the preparation the active pharmaceutical ingredient named Clomiphene and, in particular, trans-Clomiphene.Clomiphene is an active pharmaceutical ...

METHODS FOR THE PREPARATION OF HIV ATTACHMENT INHIBITOR PIPERAZINE PRODRUG COMPOUND

A method for making the compound 2. The process of claim 1 , wherein said first solvent is selected from the group of NMP claim 1 , DMSO claim 1 , MeCN claim 1 , MeOH claim 1 , acetone and a carboxylic acid.34. and . (canceled) This application is a divisional application of U.S. Ser. No. 13/760,526 filed Feb. 6, 2013, now allowed, which claims the benefit of U.S. Provisional Application Ser. No. 61/596,362 filed Feb. 8, 2012, which is herein incorporated by reference in its entirety.The invention relates to methods of making HIV attachment inhibitor compounds useful as antivirals, and in particular, to methods of making the piperazine prodrug compound identified as 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-piperazine. The invention also relates to the compounds, including intermediates, obtained by the processes herein set forth.HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with tens of millions of people still infected worldwide at the end of 2011. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2005, for example, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the treatment of HIV include nucleoside reverse transcriptase (RT) inhibitors or approved single pill combinations: zidovudine (or AZT or RETROVIR®), didanosine (or VIDEX®), stavudine (or ZERIT®), lamivudine (or 3TC or EPIVIR®), zalcitabine (or DDC or HIVID®), abacavir succinate (or ZIAGEN®), Tenofovir disoproxil fumarate salt (or VIREAD®), emtricitabine (or FTC or EMTRIVA®), COMBIVIR® (contains-3TC plus AZT), TRIZIVIR® (contains abacavir, lamivudine, and zidovudine), EPZICOM® (contains abacavir and lamivudine), TRUVADA® (contains VIREAD® and EMTRIVA®); non-nucleoside reverse transcriptase inhibitors: nevirapine (or VIRAMUNE®), delavirdine (or RESCRIPTOR®) and ...

Quaternary ammonium compounds as fuel or lubricant additives

A quaternary ammonium compound which is the reaction product of: (a) a tertiary amine having a molecular weight of less than 1000; (b) an acid-activated alkylating agent; and (c) a diacid including an optionally substituted hydrocarbyl moiety having at least (5) carbon atoms.

Molybdenum Containing Hydrosilylation Reaction Catalysts and Compositions Containing the Catalysts

A composition contains (A) a hydrosilylation reaction catalyst and (B) an aliphatically unsaturated compound having an average, per molecule, of one or more aliphatically unsaturated organic groups capable of undergoing hydrosilylation reaction. The composition ′ capable of reacting via hydrosilylation reaction to form a reaction product, such as a silane, a gum, a gel, a rubber, or a resin. Ingredient (A) contains a metal-ligand complex that can be prepared by a method including reacting a metal precursor and a ligand.

Synthesis method of hydroxybenzylamine

The present invention relates to a synthesis method of hydroxybenzylamine, belonging to the technical field of organic synthesis. The principle of the method is a demethylation reaction of methoxybenzylamine in the presence of hydrobromic acid. The present invention has the characteristics that methoxybenzylamine and hydrobromic acid are distilled at reflux to remove redundant water to improve a reaction temperature and increase the concentration of hydrobromic acid in a reaction mixture, thereby enhancing the demethylation of hydrobromic acid on methoxybenzylamine and then shortening a reaction time and increasing a conversion rate; when generation of a methyl bromide gas is not observed, distillation is continued, excess hydrobromic acid is recycled to further improve the reaction temperature and increase the conversion rate and meanwhile reduce the consumption of raw material hydrobromic acid and decrease the processing capacity of the subsequent steps and the consumption of raw material sodium hydroxide.

METHODS FOR PRODUCING POLYCYCLIC AROMATIC AMINOPHENOL COMPOUND AND RESIN COMPOSITION, AND POLYCYCLIC AROMATIC AMINOPHENOL COMPOUND, RESIN COMPOSITION, AND CURED PRODUCT

A task is to provide a method for producing a polycyclic aromatic aminophenol compound through a reduced number of steps at a low cost with high safety. The method for producing a polycyclic aromatic aminophenol compound includes the step of reacting a compound represented by the general formula (1) below and an aromatic amino compound with each other: 2. The method according to claim 1 , wherein the Rand Rare a hydrogen atom claim 1 , and the Ris a hydroxyl group.3. The method according to claim 1 , wherein the reaction in the step uses no catalyst.8. A resin composition comprising the polycyclic aromatic aminophenol compound according to and a thermosetting resin.9. The resin composition according to claim 8 , wherein the thermosetting resin is an epoxy resin and/or a maleimide resin.10. A cured product comprising a product obtained by curing the resin composition according to .11. The method according to claim 2 , wherein the reaction in the step uses no catalyst.12. A resin composition comprising the polycyclic aromatic aminophenol compound according to and a thermosetting resin.13. A resin composition comprising the polycyclic aromatic aminophenol compound according to and a thermosetting resin.14. The resin composition according to claim 12 , wherein the thermosetting resin is an epoxy resin and/or a maleimide resin.15. The resin composition according to claim 13 , wherein the thermosetting resin is an epoxy resin and/or a maleimide resin.16. A cured product comprising a product obtained by curing the resin composition according to .17. A cured product comprising a product obtained by curing the resin composition according to .18. A cured product comprising a product obtained by curing the resin composition according to .19. A cured product comprising a product obtained by curing the resin composition according to .20. A cured product comprising a product obtained by curing the resin composition according to . The present invention relates to a method for ...

PROCESS FOR MONO N-ALKYLATION OF AMINOPHENOL

The invention relates to a process for the preparation of a compound represented by formula (I) wherein X is selected from the group consisting of —H, -halogen, linear or branched C1-C7 alkyl group, linear or branched C1-C5 alkoxy group, —NOand —CN and Y is a linear or branched C1-C7 alkyl group, comprising the steps of: 10 a) reacting a compound represented by formula (II) with a compound represented by (III) to obtain an intermediate product, wherein X is as defined with respect to formula (I), wherein Z is H, CHor CH, b) reacting the intermediate product of step a) with a compound represented by YSO(IV) wherein Y is as defined with respect to formula (I) to obtain a salt and c) hydrolyzing the salt of step b) to obtain the compound of formula (I). 2. The process according to claim 1 , wherein the —OH group is ortho with respect to the carbon atom to which the nitrogen atom is attached in compound (II).3. The process according to claim 1 , wherein X is —H or a linear or branched C1-C7 alkyl group in compound (II).4. The process according to claim 1 , wherein Z is —H in compound (III).5. The process according to claim 1 , wherein step a) is performed in the presence of a reagent for nitration of an aromatic compound.6. The process according to claim 1 , wherein Y is —CH3 or —C2H5 in compound (IV).7. The process according to claim 1 , wherein step b) is performed in the presence of an organic solvent.8. The process according to claim 1 , wherein step c) is performed by the addition of HCl solution to the salt of step b).9. The process according to claim 5 , wherein the aromatic compound is copper (II) nitrate.10. The process according to claim 6 , wherein Y is —CH3 in compound (IV).11. The process of claim 7 , wherein the organic solvent is toluene. The present invention relates to a process for mono n-alkylation of an aminophenol.N-monoalkyl derivatives of aminophenols are important synthetic intermediates in organic synthesis which are used in the synthesis of ...

Organic Ligands For Templatable Mesoscale Nanocapsules

Organic ligands and methods for preparing a variety of organic ligands are provided. The subject methods provide for the preparation of organic ligands in high yield and purity for use as ligands for attachment to nanoparticles to enable the formation of three dimensional nanocapsules of stably associated organic ligand-functionalized nanoparticles. Compositions that include these nanocapsules, as well as methods of making the nanocapsules are also provided. 4. The organic ligand of any one of - , wherein Rand Rare each C-Calkoxy and n is 1.9. The organic ligand of any one of - , wherein Ris C-Calkoxy.10. The organic ligand of any one of - , wherein Ris C-Calkoxy.11. The organic ligand of any one of - , wherein X is an amine group.12. The organic ligand of any one of - , wherein X is a thiol group.19. The method of claim 16 , wherein the coupling is catalyzed by a palladium catalyst.20. The method of claim 16 , wherein Rare both hydroxyl groups.21. The method of or claim 16 , wherein the leaving group is a halogen.22. The method of or claim 16 , wherein the leaving group is a tosylate.23. A nanocapsule comprising organic ligand-functionalized nanoparticles claim 16 , wherein the organic-ligand has a structure according to any one of -.24. The nanocapsule of claim 23 , wherein the nanocapsule has a spherical surface.25. The nanocapsule of claim 23 , wherein the structure has a dimension of 0.01 μm to 10 μm.26. The nanocapsule of claim 24 , wherein the spherical surface has an average diameter of 0.01 μm to 10 μm.27. The nanocapsule of any of - claim 24 , wherein the nanoparticles have an average diameter of 1 nm to 100 nm.28. The nanocapsule of any one of - claim 24 , wherein the nanoparticles are composed of a material selected from a semiconductor material claim 24 , a metal claim 24 , a metal oxide claim 24 , a metalloid claim 24 , a metal coated material claim 24 , an oxide claim 24 , a magnetic material claim 24 , a nanosome claim 24 , a dielectric material and ...

METHOD FOR PRODUCING POLYALKYLENE GLYCOL DERIVATIVE HAVING AMINO GROUP AT END

A method simply produces a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end without using a heavy metal catalyst. A method for producing a polyalkylene glycol derivative having an amino group at the end by reacting a compound represented by the general formula (V) with an alkylene oxide, then reacting a reaction product with an electrophile represented by the general formula (I), and deprotecting the obtained product without using a heavy metal: 3. The method according to claim 2 , wherein the electrophile used in the [Step 3] and represented by the general formula (I) is at least any one of the following (I-I) to (I-IV):{'sub': A', 'A', '3, 'sup': 1a', '1b', '1', '1', '1', '1, '(I-I) an electrophile in the case in which Rand/or Rin the general formula (I) are a protective group having a structure represented by Si(R)(wherein Reach independently represent a linear monovalent hydrocarbon group having 1 to 6 carbon atoms, or a branched or cyclic monovalent hydrocarbon group having 3 to 6 carbon atoms, and Rmay bind to each other to form a 3 to 6 membered ring together with a silicon atom having bonds with R);'}{'sub': A', 'A', 'A', 'A, 'sup': 1a', '1b', '6', '6, '(I-II) an electrophile in the case in which Rand/or Rin the general formula (I) are a protective group having a structure represented by ROCO (wherein Rrepresents a residue of a hydrocarbon having 1 to 20 carbon atoms, and the residue may comprise a halogen atom, an oxygen atom, a nitrogen atom, a sulfur atom, a silicon atom, phosphorus atom, or a boron atom);'}{'sub': A', 'A, 'sup': 1a', '1b, '(I-III) an electrophile in the case in which Rand Rin the general formula (I) bind to each other to represent a cyclic protective group forming a ring together with a nitrogen atom of the amino group; and'}{'sub': A', 'A, 'sup': 1a', '1b, '(I-IV) an electrophile in the case in which Rand/or Rin the general formula (I) represent a protective group selected from the ...

Process for the Preparation of 2-Alkoxymethyl-1,4-Benzenediamines

A process for synthesizing 2-methoxymethyl-1,4-benzenediamine (V-a), its derivatives of formula (V) and the salts thereof, which comprises a radical halogenation step of formula (II). The final product can be 2-methoxymethyl-1,4-benzenediamine of formula (IV-a). 6. The process according to claim 4 , wherein the amine protection step a) claim 4 , radical halogenation step b) claim 4 , alkylating step c) and deprotection step d) are performed successively. A process to synthesize 2-alkoxymethyl-1,4-benzenediamines (V), its derivatives, and salts thereof, comprising the protection of sensitive amine functionalities, radical halogenation mediated by halogenating agents, and alkoxylation. These compounds may be used as couplers and/or primary intermediates in compositions for dyeing keratin fibers.CA 2,576,189 discloses the application of combinations of 2-methoxymethyl-1,4-benzenediamine (V-a) with various couplers and primary intermediates in oxidative dyeing compositions. U.S. Pat. No. 2,273,564 discloses a process to synthesize substituted 1,4-benzenediamine compounds with a substituent on the 2 position. U.S. Pat. No. 6,648,923 B1 discloses a process to synthesize 2-methoxymethyl-1,4-benzenediamine and the salts thereof.The previous syntheses described above to reach 2-alkoxymethyl-1,4-benzenediamines, their derivatives, and salts thereof are not completely satisfactory.Therefore, there is a need for a simple, industrially applicable, efficient, not expensive and high yield process to synthesize 2-alkoxymethyl-1,4-benzenediamines, their derivatives of formula (V), and salts thereof.The key step of the process of this invention is a radical halogenation of the N-protected- or the N,N′diprotected-2-methyl-1,4-benzenediamine derivatives of formula (II) as key intermediates.A new process has now been developed to synthesize 2-alkoxymethyl-1,4-benzenediamines (V), its derivatives, and salts thereof, which permits a production of said compounds in a novel, high yield, ...

METHOD FOR PRODUCTION OF F-18 LABELED A-BETA LIGANDS

This invention relates to improved methods, which provide access to [F-18]fluoropegylated (aryl/heteroaryl vinyl)-phenyl methyl amine derivatives. 2. A method according to claim 1 , wherein the alcohol is selected from the group consisting of ethanol or 2-propanol.3. A method according to claim 2 , wherein the alcohol is ethanol.4. A method according to claim 1 , wherein the [18F]fluoride is trapped on an anion exchange resin.5. A method according to claim 4 , wherein in step 1 a fluorinating agent is prepared by eluting [18F]fluoride trapped on a anion exchange resin using a mixture of kryptofix 2.2.2 claim 4 , potassium carbonate claim 4 , water and a C2-C3 alcohol having a boiling point between 75° C. and 85° C. followed by evaporation of the solvents.6. A method according to claim 1 , wherein in step 1 a fluorination agent is prepared by eluting [18F]fluoride trapped on a QMA resin using a mixture of kryptofix 2.2.2 claim 1 , potassium carbonate claim 1 , water and ethanol followed by evaporation of the solvents.7. A method according to claim 1 , wherein in step 1 a fluorination agent is prepared by eluting [18F]fluoride trapped on a QMA using a mixture of kryptofix 2.2.2 claim 1 , potassium carbonate claim 1 , ethanol or 2-propanol and water followed by evaporation of the solvents.8. A method according to claim 1 , wherein in step 1 a fluorination agent is prepared by eluting [18F]fluoride trapped on a QMA using a mixture of kryptofix 2.2.2 claim 1 , potassium carbonate claim 1 , ethanol and water followed by evaporation of the solvents.9. A method according to claim 1 , wherein PG is selected from the group consisting of:a) Boc,b) Trityl andc) 4-Methoxytrityl.10. A method according to claim 1 , wherein LG is selected from the group consisting of:a) Halogen andb) Sulfonyloxy,Halogen is chloro, bromo or iodo.11. A method according to claim 10 , wherein Sulfonyloxy is selected from the group comprising:a) Methanesulfonyloxy,b) p-Toluenesulfonyloxy,c) (4- ...

METHOD FOR THE METHYLATION OF NITROGEN-CONTAINING ORGANIC COMPOUNDS

A method for the methylation of amines, amides and imines comprises the step of reacting these compounds with COand Hin the presence of a Ruthenium-phosphine complex. 1. A method for the N-methylation of nitrogen-containing compounds comprising the step of:{'sub': 2', '2, 'a) reacting the nitrogen-containing organic compound with COand Hin the presence of a Ruthenium-Phosphine-complex.'}2. The method according to claim 1 , wherein step a) is performed under acidic conditions.3. The method according to claim 1 , wherein the Phosphine in the Ruthenium-Phosphine-Complex is a Tris(hetero)aryl and/or Bis(hetero)arylalkyl Phosphine.4. The method according to one of claim 1 , wherein the Ruthenium-Phosphine-Complex comprises a bisphosphororganic component claim 1 , trisphosphororganic or higher phosphororganic component.5. The method according to claim 1 , wherein step a) is performed under acidic conditions whereby the (initial) concentration of acid is ≧0.5 times the concentration of Ruthenium (in mol:mol).6. The method according to claim 5 , wherein step a) is performed under acidic conditions whereby the acid is selected out of the group comprising sulfonic acids claim 5 , especially methanesulfonic acid claim 5 , trifluormethansulfonic acid claim 5 , p-toluolsulfonic acid claim 5 , p-bromobenzosulfonic acid claim 5 , p-nitrobenzosulfonic acid claim 5 , sulfuric acid claim 5 , hydrochloric acid claim 5 , hydrofluoric acid claim 5 , trifluoracetic acid claim 5 , perchloric acid claim 5 , bis(trifluoromethane)sulfonimide or mixtures thereof.7. The method according to claim 1 , wherein step a) is carried out at an initial hydrogen pressure of ≧1 bar.8. The method according to claim 1 , wherein step a) is carried out at an initial COpressure of ≧1 bar.9. The method according to claim 1 , wherein the initial pressure ratio of H:COis ≧0.5:1 to ≧5:1.10. The method according to claim 1 , wherein step a) is carried out in a dipolar protic or aprotic solvent or in CO. This ...

NOVEL CRYSTALLINE FORMS OF PEMETREXED TROMETHAMINE SALTS

The present invention is directed to novel crystalline forms of pemetrexed tromethamine salts and processes for preparation thereof. 1. A crystalline pemetrexed tromethamine (1:2) salt.2. The crystalline pemetrexed tromethamine (1:2) salt of characterized by the PXRD as shown in .3. The crystalline form according to characterized by an X-ray Powder Diffraction Pattern having peaks at about 6.9±0.2 claim 2 , 8.8±0.2 claim 2 , 9.8±0.2 claim 2 , 11.1±0.2 claim 2 , 13.9±0.2 claim 2 , 16.3±0.2 claim 2 , 17.25±0.2 claim 2 , 18.4±0.2 claim 2 , 19.2±0.2 claim 2 , 22.0±0.2 claim 2 , 23.7±0.2 claim 2 , and 29.4±0.2 (2θ degrees).4. The crystalline pemetrexed tromethamine (1:2) salt of characterized by the PXRD as shown in .5. The crystalline form according to characterized by an X-ray Powder Diffraction Pattern having peaks at about 9.1±0.2 claim 4 , 10.2±0.2 claim 4 , 11.1±0.2 claim 4 , 12.9±0.2 claim 4 , 14.5±0.2 claim 4 , 16.2±0.2 claim 4 , 16.9±0.2 claim 4 , 17.7±0.2 claim 4 , 18.7±0.2 claim 4 , 19.2±0.2 claim 4 , 19.6±0.2 claim 4 , 19.9±0.2 claim 4 , 20.4±0.2 claim 4 , 21.3±0.2 claim 4 , 23.1±0.2 claim 4 , 23.5±0.2 claim 4 , and 25.9±0.2 (2θ degrees).6. The crystalline pemetrexed tromethamine (1:2) salt of characterized by the PXRD as shown in .7. The crystalline form according to characterized by an X-ray Powder Diffraction Pattern having peaks at about 9.3±0.2 claim 6 , 10.4±0.2 claim 6 , 11.2±0.2 claim 6 , 13.1±0.2 claim 6 , 14.6±0.2 claim 6 , 16.3±0.2 claim 6 , 17.0±0.2 claim 6 , 17.6±0.2 claim 6 , 18.2±0.2 claim 6 , 18.9±0.2 claim 6 , 19.4±0.2 claim 6 , 20.0±0.2 claim 6 , 21.5±0.2 claim 6 , 23.2±0.2 claim 6 , 23.5±0.2 claim 6 , 25.2±0.2 claim 6 , 25.6±0.2 claim 6 , 26.0±0.2 claim 6 , 26.2±0.2 claim 6 , 27.6±0.2 claim 6 , and 31.1±0.2 (2θ degrees).8. The crystalline pemetrexed tromethamine (1:2) salt of characterized by the PXRD as shown in .9. The crystalline form according to characterized by an X-ray Powder Diffraction Pattern having peaks at about 4.9±0.2 claim 8 ...

4-alkoxy-3-(trifluoromethyl)benzyl alcohol production method

The present invention relates to a production method of 4-alkoxy-3-trifluoromethylbenzyl alcohol at a high conversion ratio, which can strictly suppress production of a byproduct by using DIBAL as a reducing agent.

METHOD FOR THE SELECTIVE PRODUCTION OF N-METHYL-PARA-ANISIDINE

The invention “Method for selective synthesis of N-methyl-para-anisidine” relates to chemical technology processes, namely to catalytic alkylation of aromatic amines and nitro compounds. 1. The process for synthesis of N-methyl-para-anisidine , consist in that N-alkylation of para-nitroanisole and/or para-anisidine is performed in vapor phase on dehydrogenating catalyst at a temperature 180-260° C. and atmospheric pressure with subsequent product isolation using rectification.2. The process of wherein N-methyl-para-anisidine is produced claim 1 , correspondingly claim 1 , from para-nitroanisole.3. The process of wherein N-methyl-para-anisidine is produced claim 1 , correspondingly claim 1 , from para-anisidine.4. The process of wherein N-alkylation is performed in nitrogen stream.5. The process of wherein N-alkylation is performed in hydrogen stream.6. The process of wherein the catalyst has the following composition: CuO—55%; ZnO—10.5%; CrO—13.5%; AlO0 the rest.7. The process of wherein the catalyst has the following composition CuO—25%; ZnO—25%; CaO—5%; AlO—the rest.8. The process of wherein the catalyst has the following composition: CuO—25-45%; BaO—2-10%; TiO—15-35%; CrO—the rest.9. The process of wherein the catalyst has the following composition: CuO—35-45%; ZnO—25-35%; NiO—3-8%; AlO—the rest.10. The process of wherein the catalyst has the following composition: CuO—12-19% MnO—2-3%; CrO—1.0-1.4%; FeO—1.0-1.4%; CoO—0.5-0.8%; AlO—the rest.11. The process of wherein Raney nickel catalyst is used.12. The process of wherein BASF Cu-E403TR catalyst is used with the following composition: copper chromite—67-71% claim 6 , copper—11-15% claim 6 , copper oxide—8-21% claim 6 , graphite—0-4% claim 6 , chromium (3+) oxide—0-3%.13. The process of wherein BASF Cu-0203T 1/8 catalyst is used with the following composition: copper oxide—75-100% claim 6 , chromium (3+) oxide—0.1-1%.14. The process of wherein BASF Cu-E406 TR catalyst is used with the following composition: Cu—36% ...

N-heterocyclic carbene type palladium catalyst and its preparation method as well as applications

The present invention relates to an n-heterocyclic carbene (NHC) type palladium catalyst and its preparation method as well as applications. Its preparation process is as below: select glyoxal as the raw material to synthesize glyoxaldiimine in the presence of Lewis acid or Bronsted acid, and then react with paraformaldehyde to get the NHC type ligand. Use palladium (II) to react with the compound containing carbon-nitrogen double bonds to get palladium (II) cyclic dimer; make the palladium cyclic dimer and the NHC type ligand coordinated to get the NHC type palladium catalyst. The palladium catalyst with a brand new structure according to the present invention, boasts high activity and multi-purpose. In addition, it shows excellent reaction activity in a lot of catalytic-coupling reactions including Suzuki-Miyaura, Heck, Buchwald-Hartwig, Kumada-Tamao-Corriu, Sonogashira, Negishi and α-ketone arylation reactions, and some reactions even can be carried out with the presence of an extremely low concentration of catalyst, exhibiting favorable industrialization prospect.

Method for producing 2-(isopropylamino)ethanol

The present invention relates to a method of producing 2-(isopropylamino)ethanol, including subjecting acetone, 2-aminoethanol, and hydrogen to a vapor-phase catalytic reaction in the presence of a noble metal-containing catalyst. According to the present invention, 2-(isopropylamino)ethanol can be industrially obtained in a large amount and with high efficiency through the vapor-phase catalytic reaction of acetone, 2-aminoethanol, and hydrogen. 2-(Isopropylamino)ethanol is a compound useful as a raw material for a drug, an agricultural chemical, or the like.

METHOD FOR THE PREPARATION OF 1-ARYL-1-ALKYL-2-ALKYL-3-DIALKYLAMINOPROPANE COMPOUNDS

The present invention refers to the preparation of 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds, such as tapentadol, using a diastereoselective Eschenmoser-Claisen or Ireland-Claisen rearrangement. 4. A method according to claim 1 , wherein Ar is selected from the group consisting of 3-hydroxy-phenyl claim 1 , 3-methoxyphenyl claim 1 , 3-benzyloxyphenyl claim 1 , and O-protected 3-hydroxyphenyl.5. A method according to claim 1 , wherein R1 is selected from the group consisting of ethyl claim 1 , ethenyl claim 1 , propyl claim 1 , propenyl claim 1 , iso-propyl claim 1 , iso-propenyl claim 1 , butyl claim 1 , butenyl claim 1 , iso-butyl claim 1 , and iso-butenyl claim 1 , and is preferably an ethyl or an ethenyl group.6. A method according to claim 1 , wherein R2 is selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , iso-propyl claim 1 , butyl claim 1 , and iso-butyl claim 1 , and is preferably a methyl group.7. A method according to claim 1 , wherein R3 and R4 are independently of one another selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , iso-propyl claim 1 , butyl claim 1 , iso-butyl claim 1 , and optionally substituted benzyl.12. (canceled) The present invention refers to a novel method for the preparation of 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds involving an Eschenmoser-Claisen or an Ireland-Claisen rearrangement.Among the known 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds, 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methyl-propyl]phenol (tapentadol) is probably the most famous. Tapentadol (formula IXa; see below) is a centrally acting analgesic with a dual mode of action as an agonist at the μ-opioid receptor and as a norepinephrine reuptake inhibitor. It is generally used for the treatment of moderate to grave acute pain.To date, several methods for the preparation of tapentadol and other 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds are ...