Method of preparing 1-chloroacetamido-1,3,3,5,5-pentamethylcyclohexane

Method of preparing 1-chloroacetamido-1,3,3,5,5-pentamethylcyclohexane, an intermediate in the synthesis of 1-amino-1,3,3,5,5-pentamethylcyclohexane (Neramexane) or a pharmaceutically acceptable salt thereof, comprising step (iii): (iii) reacting 1-hydroxy-1,3,3,5,5-pentamethylcyclohexane with chloroacetonitrile in the presence of an acid, wherein 1-hydroxy-1,3,3,5,5-pentamethylcyclohexane is employed in step (iii) as obtained in the reaction of a methylmagnesium halide with 3,3,5,5-tetramethylcyclohexanone without having been subjected to a purification step.

Novel compound and method for preparing the same

The invention is directed to a compound represented by the Formula (1) as defined herein, and a method for preparing a compound represented by the Formula (1) which includes: reacting a diamine compound represented by the Formula (2) as defined herein with a methacrylic anhydride or an acrylic anhydride under a condition where an organic acid having a pKa of 2.0 or more is present in an amount of 0.5 to 5.0 moles based on 1 mole of the diamine compound to obtain a reaction mixture; adding phosphoric acid to the reaction mixture; and purifying the reaction mixture by extraction with an organic solvent.

18ß-GLYCYRRHETINIC ACID DERIVATIVES AND SYNTHETIC METHOD THEREOF

The present invention provides a chemical compound having the structure being one selected from a group consisting of 2. The method according to further comprising a step of using an isopropylamine solution as the amine solution when Ris CONHCH(CH) claim 1 , and using an aniline solution as the amine solution when Ris CONHCH.3. The method according to further comprising steps of:methylating the 18β-glycyrrhetinic acid to obtain a methylated 18β-glycyrrhetinic acid; andoxidizing the methylated 18β-glycyrrhetinic acid to obtain a second compound.4. The method according to further comprising a step of esterifying the lactone compound to obtain a first derivative of the lactone compound.5. The method according to further comprising a step of cleaving a lactone ring of the lactone compound to obtain a second derivative of the lactone compound.6. The method according to further comprising a step of treating the second derivative with an alcohol solution to obtain a third derivative of the lactone compound.7. The method according to claim 6 , wherein the alcohol solution is one of an isopropyl alcohol solution and a benzyl alcohol solution.8. The method according to further comprising a step of esterifying the second compound with an alcohol solution to obtain a fourth derivative of the lactone compound.9. The method according to further comprising a step of cleaving a lactone ring of the fourth derivative by an acidic solution to obtain a fifth derivative of the lactone compound.13. The method according to claim 12 , wherein the chemical compound with Rbeing one of CONHCH(CH)and CONHCHis obtained by steps of:oxidizing the 18β-glycyrrhetinic acid to form a first compound;treating the first compound with an m-chloroperbenzoic acid to afford a lactone compound; andtreating the lactone compound with an amine solution to obtain the chemical compound being a first derivative of the chemical compound.14. The method according to further comprising a step of using an ...

METHOD FOR PREPARING ALKYL LACTATE AND A METHOD FOR PREPARING LACTAMIDE USING THE SAME

This disclosure relates to a method for preparing alkyl lactate with high yield and high selectivity, comprising the step of reacting glycerol with water or alcohol in the presence of a catalyst. 2. The method according to claim 1 , wherein the catalyst is a homogeneous or heterogeneous catalyst.3. The method according to claim 2 , wherein the homogeneous catalyst is at least one selected from the group consisting of an alkali metal compound having a hydroxyl or alkoxy group claim 2 , a bicarbonate (HCO)-containing metal compound claim 2 , and a carbonate (CO)-containing metal compound.4. The method according to claim 3 , wherein the alkali metal compound having a hydroxyl group is NaOH claim 3 , KOH claim 3 , LiOH or Ba(OH) claim 3 , andthe alkali metal compound having an alkoxy group is NaOR, KOR or LiOR (wherein, R is a substituted or unsubstituted C1-10 alkyl group).5. The method according to claim 2 , wherein the heterogeneous catalyst is a metal compound containing Mg claim 2 , Ca claim 2 , Zr claim 2 , Sn or Ti.6. The method according to claim 5 , wherein the heterogeneous catalyst further comprises at least one selected from the group consisting of an alkali metal compound claim 5 , a hydroxyl group-containing metal compound claim 5 , a bicarbonate-containing metal compound claim 5 , a carbonate-containing metal compound claim 5 , activated clay claim 5 , zeolite claim 5 , active carbon claim 5 , diatomaceous earth claim 5 , bentonite claim 5 , alumina claim 5 , silicalite claim 5 , fly ashes claim 5 , molecular sieve claim 5 , vermiculite claim 5 , perlite claim 5 , π-complex compound adsorbent claim 5 , clay and polymer resin.7. The method according to claim 1 , wherein the reaction is conducted in a batch reactor or tubular reactor.8. The method according to claim 1 , wherein the reaction is conducted at a temperature of 100 to 300° C. and a pressure of 10 to 200 atm for 1 to 20 hours claim 1 , under inert atmosphere.9. The method according to claim 1 , ...

PROCESS FOR THE PREPARATION OF LACOSAMIDE

The present invention relates to a novel and improved process for the preparation of lacosamide, wherein the process is a sequential one-pot process. 2. The process as claimed in claim 1 , wherein all the reactions of step a) to d) are carried out in dicholormethane.3. The process as claimed in claim 1 , wherein the condensation of N-Boc-D-serine with benzylamine in step a) is performed using a coupling agent claim 1 , optionally in the presence of catalytic 1-hydroxybenzitriazole4. The process as claimed in claim 3 , wherein the coupling agent is selected from the group consisting of (benzotriazole- 1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) claim 3 , is obutyl chloroformate claim 3 , N claim 3 ,N′-dicyclohexylcarbodiimide (DCC) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide(EDC).5. The process as claimed in claim 1 , wherein methylation of compound of formula I in step b) is carried out using a methylating agent in a biphasic system in presence of a phase transfer catalyst.6. The process as claimed in claim 5 , wherein the methylating agent is selected from the group consisting of dimethyl sulfate claim 5 , methyl triflate claim 5 , and trimethyl phosphate.7. The process as claimed in claim 6 , wherein the methylating agent is dimethyl sulfate.8. The process as claimed in claim 5 , wherein the aqueous phase of the biphasic system contains an inorganic base.9. The process as claimed in claim 8 , wherein the inorganic base is selected from an alkali metal hydroxide claim 8 , carbonate and bicarbonate.10. The process as claimed in claim 5 , wherein the phase transfer catalyst is selected from a quarternized amine salt or a phosphonium salt.11. The process as claimed in claim 10 , wherein quarternized amine salt is selected from the group consisting of sulfate claim 10 , chloride or bromide salts of tetraalkylammonium; benzyltrialkylammonium halides; cetyltrialkylammonium halides and Tweens (polyoxyethylene sorbitan esters) such as Tween®20 ...

PHENYL-N-ACYL DERIVATIVES OF AMINES AND AMINO ACIDS, A PROCESS FOR THE PREPARATION THEREOF, A PHARMACEUTICAL COMPOSITION AND USE THEREOF

The present invention relates to novel phenyl-N-acyl derivatives of biogenic amines and amino acids of general formula (I) as cyclooxynease inhibitors, possessing analgetic and anti-inflammatory properties and devoid of side effects in particular ulcerogeneity and pro-spasmodic actions, as well as capability to potentiate effect of other analgetics, and possessing in addition antihypoxic, antidepressant and anti-Parkinsonistic action; as well as to the processes for the preparation novel and known phenyl-N-acyl derivatives of biogenic amines, to a pharmaceutical composition and to an agent comprising compounds of general formula (I) as well as to use thereof and a method of treating. 2. The process according to claim 1 , wherein 1-1.2 equivalents of diphenylphosphorylazide and triethylamine are used.3. The process according to claim 1 , wherein as amino derivatives tyrosine or phenylalanine esters are used.43. The process according to any one of - claims 1 , wherein as an organic solvent N claims 1 ,N-dimethylformamide or ethylacetate are used.53. The process according to any one of - claims 1 , which is conducted at the temperature ranging from −25° C. to 0° C.7. The process according to claim 6 , wherein as amino derivatives tyrosine or phenylalanine esters are used. This application is a divisional of co-pending U.S. application Ser. No. 11/886,965, filed on Oct. 23, 2008, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2006/000139 (published as WO 2006/101422 A1), filed Mar. 24, 2006, which claims priority to Application RU 2005108492, filed Mar. 25, 2005. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The present invention relates to the field of bioorganic chemistry and concerns novel compounds, phenyl-N-acyl derivatives of biogenic amines as well as a process for synthesis of novel and known ...

METHOD FOR SYNTHESIZING RARE EARTH METAL EXTRACTANT

A rare earth metal extractant containing, as the extractant component, dialkyldiglycol amide acid which is excellent in breaking down light rare earth elements is reacted in diglycolic acid (X mol) and an esterification agent (Y mol) at a reaction temperature of 70° C. or more and for a reaction time of one hour or more such that the mol ratio of Y/X is 2.5 or more, and is subjected to vacuum concentration. Subsequently, a reaction intermediate product is obtained by removing unreacted products and reaction residue. Then a nonpolar or low-polar solvent which is an organic solvent for forming an organic phase during solvent extraction of the rare earth metal and which is capable of dissolving dialkyldiglycol amide acid is added as the reaction solvent, and the reaction intermediate product is reacted with dialkyl amine (Z mol) such that the mol ratio of Z/X is 0.9 or more. 2. A method for synthesizing a rare earth metal extractant according to wherein the esterifying agent is selected from acetic anhydride and trifluoroacetic anhydride.3. A method for synthesizing a rare earth metal extractant according to wherein the organic solvent to form an organic phase during solvent extraction of rare earth metals is selected from the group consisting of toluene claim 1 , xylene claim 1 , hexane claim 1 , isododecane claim 1 , kerosene claim 1 , and higher alcohols.4. A method for synthesizing a rare earth metal extractant according to wherein in the step of reacting diglycolic acid with an esterifying agent claim 1 , the molar ratio of Y/X is in the range: 2.5≦Y/X≦6.5.5. A method for synthesizing a rare earth metal extractant wherein in the step of reacting the reaction intermediate product with a dialkylamine claim 1 , the molar ratio of Z/X is in the range: 0.9≦Z/X≦1.2.6. A method for synthesizing a rare earth metal extractant wherein the reaction solvent is added in such an amount that the dialkyl diglycol amic acid formed after the reactions may be present in a ...

NOVEL COMPOUND ACCELERATING SECRETION OF HUMAN-DERIVED ANTI-MICROBIAL PEPTIDE, METHOD FOR PREPARING SAME, AND COMPOSITION HAVING SAME AS ACTIVE INGREDIENT

Disclosed is a compound having an acceleration effect on the secretion of human β-defensin, LL-37, which is a human-derived anti-microbial peptide, a method for preparing same, and a composition for accelerating the secretion of anti-microbial peptide having same as an active ingredient, and the compound and the composition using same of the present invention enhance the anti-microbial effect and the immunity control effect that the anti-microbial peptide has in the body by accelerating the secretion of the anti-microbial peptide in the body. 18-. (canceled)10. The new compound of claim 9 , wherein the antimicrobial peptides are human β-defensin-2 claim 9 , β-defensin-3 claim 9 , or LL-37.14. The composition of claim 13 , wherein the compound as an active ingredient is contained at 0.001-90 wt %.15. The composition of claim 13 , wherein the composition for promoting secretion of human antimicrobial peptides in vivo is a formulation selected from the group consisting of a liquid phase claim 13 , an emulsion phase claim 13 , a suspension phase claim 13 , a cream phase claim 13 , an ointment phase claim 13 , a gel phase claim 13 , a jelly phase claim 13 , and a spray phase.16. The composition of claim 13 , wherein the composition for promoting secretion of human antimicrobial peptides in vivo is a formulation selected from the group consisting of a tablet claim 13 , a liquid claim 13 , a powder claim 13 , and an injection. This application is a continuation application of PCT International Application No. PCT/KR2010/005759 filed Aug. 27, 2010, the contents of which are incorporated herein by reference in their entirety.The following disclosure relates to a compound for promoting the secretion of human antimicrobial peptides, and more particularly, to a new compound for inducing direct or indirect expression of human β-defensin-2 and -3 and LL-37, which are human antimicrobial peptides, a method for preparing the same, and a composition comprising the same as an active ...

Process for Preparing Esteramide Compounds

The present invention concerns a process for preparing esteramide compounds. More particularly, the invention relates to a process for preparing esteramide compounds by reaction between a diester and an amine, in the presence of a basic compound, wherein the basic compound and the amine in gaseous form are co-added to the diester, the reaction being conducted at a temperature of 30° C. or higher.

METERING RING

The present invention relates to an apparatus for metering flowable media or gases, and to the use thereof. 1. A method for carrying out a chemical reaction by continuously feeding reactants in a tubular or loop reactor , comprising metering one of the reactants through one or more metering rings located at one or more metering sites in the tubular or loop reactor , wherein at the point of metered addition , said one of the reactants is rapidly mixed and reacted with remaining reactants.2. The method of claim 1 , wherein the chemical reaction is the preparation of methacrylamide by hydrolysis of acetone cyanohydrin with concentrated sulfuric acid.3. The method of claim 2 , wherein the acetone cyanohydrin is the reactant that is fed through the one or more metering rings.4. The method of claim 2 , wherein the acetone cyanohydrin exits through the one or more metering rings in the form of a fine distribution of droplets.5. The method of claim 2 , wherein the sulfuric acid is the reactant that is fed through the one or more metering rings.6. The method of claim 2 , wherein the temperature of at least one metering ring is controlled.7. The method of claim 2 , wherein metered addition is carried out at elevated pressure.8. The method of claim 2 , wherein at least one of the metering rings has a peripheral distribution chamber.9. The method of claim 2 , wherein at least one of the metering rings has an inner wall that is permeated by a plurality of injection channels.10. The method of claim 2 , wherein at least one of the metering rings enables supply and fine distribution of the reactants over the entire circumference or cross section of the reactor.11. The method of claim 2 , wherein the metering sites project through tubes into the interior of the reactor.12. The method of claim 11 , wherein the tubes are of different length.13. The method of claim 2 , wherein the concentrated sulfuric acid is used in a molar excess to the acetone cyanohydrin claim 2 , and a reaction ...

METHOD FOR PREPARING ALISKIREN AND ITS INTERMEDIATES THEREOF

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing Rfrom the amino group and obtaining Aliskiren shown as formula I. 2. The method according to wherein the ether class solvent in step (1) is one selected from diethyl ether claim 1 , tetrahydrofuran or 1 claim 1 ,2-dimethoxyethane.3. The method according to wherein the inert solvent in step (2) is methylene chloride or tetrahydrofuran.4. The method according to wherein the ketone class solvent in step (3) is acetone or 2-butanone; and the molar ratio between lithium bromide and the compound of formula XX is 1.1 to 5.5. The method according to wherein the said ether class solvent in step (4) is either one or mixture of any two selected from diethyl ether claim 1 , tetrahydrofuran or 1 claim 1 ,2-dimethoxyethane; the said iron-contained catalyst is selected from iron(III) acetylacetonate or Iron(III) chloride; and the reaction temperature is −15° C.˜20° C.7. The method according to for preparing the Aliskiren compound of formula I claim 6 , wherein the reaction in step (a) between the compound of formula XV and the compound of formula VII to obtain the compound of formula XXIII is implemented in an inert solvent.8. The method according to for preparing the Aliskiren compound of formula I claim 7 , wherein the inert solvent is one selected from dioxane or toluene.9. ...

Process For Making Amides

Provided are processes for making an amide of a carboxylic acid by reacting an amine of the formula (I) 2. The process of claim 1 , wherein measures (a) and (b) are carried out without the use of any organic solvent.3. The process of claim 1 , wherein the reaction in measure (a) is carried out at a temperature in the range of from 130 to 230° C.4. The process of claim 1 , wherein the carboxylic acid comprises lactic acid.5. The process of claim 1 , wherein the amine according to formula (I) comprises methylamine claim 1 , dimethylamine claim 1 , ethylamine claim 1 , diethylamine claim 1 , n-propylamine claim 1 , isopropylamine claim 1 , diisopropylamine claim 1 , n-butylamine claim 1 , iso-butylamine claim 1 , tert-butylamine claim 1 , methyl n-propylamine claim 1 , n-methyl-n-ethyl amine claim 1 , or methyl iso-propylamine.6. The process of claim 1 , wherein the single reactor is connected to a fractionation column and a condenser.7. The process of claim 1 , wherein the single reactor is connected to a combination of two fractionation columns and two condensers.8. The process of claim 1 , wherein the step for re-introducing the unreacted amine according to formula (I) into the reaction mixture comprises using liquid jet nozzles.9. The process of claim 1 , wherein the carboxylic acid comprises caprylic acid claim 1 , capric acid claim 1 , or lauric acid and the amine comprises dimethylamine or diethylamine.10. The process of claim 1 , wherein the molar ratio of amine according to formula (I) to carboxylic acid is in the range of from 1.2:1 to 1:1 This application claims the benefit under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61/612,452, filed Mar. 19, 2012, which is incorporated herein by reference in its entirety.The present invention is directed towards a process for making an amide of a carboxylic acid by reacting an amine of the formula (I)H—NRR  (I)Rand Rbeing defined as being the same or different,Rbeing selected from C-C-alkyl,Rbeing selected ...

Process for the Preparation of Iosimenol

A process for the preparation of iosimenol comprising reacting 5,5′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (C-VI) with a 3-halo-1,2-propanediol in an aqueous solvent. A process for the preparation of C-VI comprising reacting 3,3′4(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) with 3-amino-1,2-propanediol in the presence of an inorganic base and a suitable non-aqueous polar solvent. A process for the preparation of C-V comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof. 121-. (canceled)23. The process of wherein the solvent further comprises a suitable ethereal solvent.24. The process of wherein the solvent optionally further comprises a suitable ethereal solvent claim 22 , and the solvent is selected from acetonitrile claim 22 , ethyl acetate claim 22 , a mixture of acetonitrile and tetrahydrofuran claim 22 , a mixture of ethyl acetate and tetrahydrofuran claim 22 , a mixture of acetonitrile and 1 claim 22 ,2-dimethoxyethane claim 22 , a mixture of ethyl acetate and 1 claim 22 ,2-dimethoxyethane claim 22 , or a mixture of acetonitrile and ethyl acetate.25. The process of wherein the solvent is selected from acetonitrile claim 24 , ethyl acetate claim 24 , a mixture of acetonitrile and tetrahydrofuran claim 24 , a mixture of ethyl acetate and tetrahydrofuran claim 24 , or a mixture of acetonitrile and ethyl acetate.26. The process of wherein the solvent comprises acetonitrile or a mixture of acetonitrile and tetrahydrofuran.27. The process of wherein the solvent is a mixture of acetonitrile and tetrahydrofuran wherein the weight ratio of acetonitrile:tetrahydrofuran is about 1:9 to about 49:1.28. The process of wherein the weight ratio of acetonitrile:tetrahydrofuran is about 1:1 to about 49:1.29. The ...

METHOD FOR PREPARING 2-AMINO-N-(2,2,2-TRIFLUOROETHYL) ACETAMIDE

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A. 2. The method of step (A) wherein the compounds of Formulae 2 and 3 and the coupling reagent are contacted in the presence of a base and a water immiscible solvent.3. The method of wherein the base is derived from the coupling reagent and the coupling reagent is N claim 2 ,N′-carbonyldiimidazole.4. The method of step (B) wherein the compound of Formulae 4 and hydrogen are contacted in the presence of a hydrogenolysis catalyst and a water immiscible solvent.5. The method of wherein the hydrogenolysis catalyst is palladium on carbon.6. The method of step (C) wherein the compound of Formula 1 is contacted with an acid of Formula 5 in the presence of a water immiscible solvent.7. The method of wherein the acid of Formula 5 comprises hydrogen chloride.8. (canceled)9. A compound which is phenylmethyl N-[2-oxo-2-[(2 claim 6 ,2 claim 6 ,2-trifluoroethyl)amino]-ethyl]carbamate.11. The method of step (A1) wherein the compounds of Formulae 8 and 3 and the coupling reagent are contacted in the presence of a base and a water immiscible solvent.12. The method of wherein the base is derived from the coupling reagent and the coupling reagent is N claim 11 ,N′-carbonyldiimidazole.13. The method of step (B1) wherein the compounds of Formulae 7 and 5 are contacted in the presence of a water immiscible solvent.14. The method of wherein the acid of Formula 5 comprises hydrogen chloride.15. (canceled) ...

AGOMELATINE INTERMEDIATES AND PREPARATION METHOD THEREOF

The present invention relates to the intermediate compounds for preparation of agomelatine, as well as the preparation methods thereof. The intermediate of the present invention for preparation of agomelatine is compound A as shown in the following formula. Also provided are two novel intermediate compounds. When we use these new intermediate compounds to prepare agomelatine, it is simple to manipulate, well-controlled and with high purity, without complicated operations such as rectification and column chromatography separation, and suitable for industrial production. Meanwhile, the preparation methods of the two new intermediates themselves is simple and high yield, only using the most commonly-used 7-methoxy-tetralone as original starting material and undergoing one step of reaction to obtain the intermediates, followed by one more step of converting the intermediate compounds to desired product agomelatine. Said reaction processes are greatly simplified, with the reaction yield being improved and the difficulty in purification of previous method being overcome, as compare with the previous technique for preparation of agomelatine. Typically, the yield of the present invention is over 70%. 116-. (canceled)20. The method according to claim 19 , wherein the metal catalyst is Raney-Ni claim 19 , the amount of which is 0.1-0.3 times the amount of the compound C by weight.21. The method according to claim 19 , wherein the amount of the acetic anhydride is 1-1.3 times the molar amount of the compound C.23. The method according to claim 22 , wherein the dehydrogenating agent used in the aromatization is dichloro-dicyanobenzoquinone.24. The method according to claim 22 , wherein the amount of dehydrogenating agent is 1-3 times the molar amount of the compound A.25. The method according to claim 22 , wherein the solvent used in the reaction is a mixture of toluene and glacial acetic acid claim 22 , a mixture of acetonitrile and glacial acetic acid claim 22 , or glacial ...

PROCESS FOR THE SYNTHESIS OF AGOMELATINE

Process for the industrial synthesis of the compound of formula (I) 120-. (canceled)23. The process according to claim 21 , wherein the compound of formula (VII) is subjected to reduction by hydrogen in the presence of Raney nickel in a medium comprising acetic anhydride in a polar protic medium to yield the compound of formula (I) claim 21 , which is isolated in the form of a solid.24. The process according to claim 21 , wherein the group Xa represents —S—C(S)—OCH.25. The process according claim 21 , to claim 21 , wherein the free radical reactions are initiated by thermal means at a temperature of from 50 to 140° C.26. The process according to claim 21 , wherein cyclisation of compound of formula (IV) is carried out at a temperature of from 130 to 135° C.27. The process according to claim 21 , wherein the step of addition of the compound of formula (II) to the compound of formula (III) and that of cyclisation of the compound of formula (IV) are initiated in the presence of dilauroyl peroxide.28. The process according to claim 21 , wherein the step of addition of the compound of formula (II) to the compound of formula (III) is carried out in chlorobenzene.29. The process according t claim 21 , wherein the step of cyclisation of the adduct of formula (IV) to form the compound of formula (V) is carried out in ethyl acetate.30. The process according to claim 21 , wherein the conversion of the compound of formula (V) into the compound of formula (VI) is carried out in the presence of aluminium isopropoxide.31. The process according to wherein the conversion of the compound of formula (V) into the compound of formula (VI) is carried out in isopropanol.32. The process according to claim 21 , a catalytic amount of p-toluenesulphonic acid is added to the mixture at the end of conversion of the compound of formula (V) into the compound of formula (VI).33. The process according to claim 21 , wherein the aromatisation of the compound of formula (VI) is carried out in the ...

METHOD OF MAKING FATTY ACID N-ACYLALKANOLAMINES

The present invention relates to methods for making a fatty acid N-acylalkanolamine having the formula: 2. The method of claim 1 , wherein the alkanolamine is selected from the group consisting of ethanolamine claim 1 , propanolamine claim 1 , isopropanolamine claim 1 , butanolamine claim 1 , isobutanolamine claim 1 , methylethanolamine claim 1 , butylethanolamine claim 1 , and mixtures thereof.3. The method of claim 1 , wherein the alkanolamine is ethanolamine.4. The method of claim 3 , wherein the fatty acid N-acylalkanolamine is a fatty acid N-acylethanolamine.5. The method of claim 1 , wherein the fatty acid contains from about 4 to about 26 carbon atoms.6. The method of claim 5 , wherein the fatty acid is an unsaturated fatty acid.7. The method of claim 6 , wherein the fatty acid is selected from the group consisting of oleic acid claim 6 , myristoleic acid claim 6 , palmitoleic acid claim 6 , sapienic acid claim 6 , elaidic acid claim 6 , vaccenic acid claim 6 , linoleic acid claim 6 , linoelaidic acid claim 6 , α-linolenic acid claim 6 , arachidonic acid claim 6 , eicosapentaenoic acid claim 6 , erucic acid claim 6 , docosahexaenoic acid claim 6 , and mixtures thereof.8. The method of claim 6 , wherein the fatty acid is oleic acid.9. The method of claim 1 , wherein said reacting is carried out in the presence of at least one solvent.10. The method of claim 9 , wherein the solvent is hexane.11. The method of claim 9 , wherein the solvent is present in a concentration ranging from 30 to 85 wt % of all total reactants.12. The method of claim 9 , wherein the solvent is present in a concentration ranging from 30 to 60 wt % of all total reactants.13. The method of claim 1 , wherein said reacting is carried out with at least one catalyst.14. The method of claim 13 , wherein the catalyst is a lipase.15. The method of claim 14 , wherein the lipase is present in a concentration ranging from 10 to 50 wt % of all total reactants.16. The method of claim 14 , wherein the ...

CONVERGENT SYNTHESIS OF RENIN INHIBITORS AND INTERMEDIATES USEFUL THEREIN

Described is a method for the preparation of renin inhibitors such as aliskiren, and intermediates useful therein. The method introduces a nitrogen-containing intermediate such as a lactone of formula (8). 3. A compound according to or , wherein Ris 2-propyl.5. A method according to claim 4 , wherein the reaction is conducted in the presence of a chiral catalyst.6. A method according to claim 5 , wherein the chiral catalyst is an enzyme.7. A method according to claim 6 , wherein the enzyme hydroxynitrile lyase. This application is a divisional of commonly owned U.S. application Ser. No. 12/810,220, filed Sep. 22, 2010 (now U.S. Pat. No. ______), which is the national phase application under 35 USC §371 of PCT/EP2008/009050, Dec. 19, 2008, which designated the US and claims benefit of EP Patent Application No. 07025093.1, filed Dec. 24, 2007, the entire contents of each of which are hereby incorporated by reference.The invention pertains to a convergent synthesis route for the preparation of certain 2(S),4(S),5(S),7(S)-2,7-dialkyl-4-hydroxy-5-amino-8-aryl-octanoyl amide derivatives, or pharmaceutically acceptable salts thereof, such as the compound aliskiren. The invention particularly relates to a synthetic route that will introduce the nitrogen of the above mentioned compounds ultimately required for the amino-group at C-5, at a relative early stage of the synthesis. The invention further relates to novel intermediates useful in the manufacture of the above mentioned compounds. Particularly, the 2(S),4(S),5(S),7(S)-2,7-dialkyl-4-hydroxy-5-amino-8-aryl-octanoyl amide derivatives to which the methods of the present invention applies are any of those having renin inhibitory activity and, therefore, pharmaceutical utility, e.g., those disclosed in U.S. Pat. No. 5,559,111, WO 2006/061427, or WO 2006/095020.The 2(S),4(S),5(S);7(S)-2,7-dialkyl-4-hydroxy-5-amino-8-aryl-octanoyl amide derivatives, or pharmaceutically acceptable salts thereof to which the invention pertains, ...

PROCESS FOR THE SYNTHESIS OF ANTIEPILEPTIC DRUG LACOSAMIDE

The present invention relates to the improved and efficient process for the synthesis of antiepileptic drug Lacosamide in high enantiopurity (>98% ee) and better yield. More particularly, the present invention relates to improved and efficient, cost effective process for synthesis of desired (R) isomer of Lacosamide starting from commercially available (S)-benzyl glycidyl ether. 2. The process as claimed in step (i) of claim 1 , wherein the base is selected from the group consisting of metal hydrides claim 1 , hydroxides claim 1 , oxides claim 1 , carbonates claim 1 , bicarbonates claim 1 , alkoxides or primary and secondary amine claim 1 , ammonia claim 1 , alkyl amine; preferably NaOH claim 1 , KOH claim 1 , NaCO claim 1 , NaHCO claim 1 , NaOCH.3. The process as claimed in step (i) of claim 1 , wherein the alcohol is selected from the group consisting of (C1-C5) alcohol claim 1 , branched alcohol claim 1 , diol claim 1 , triol claim 1 , aryl alcohol; preferably claim 1 , C1-C5-alcohols.4. The process as claimed in step (ii) of claim 1 , wherein the temperature is maintained in the range between −20° C. to 60° C. preferably −20° to 40° C.5. The process as claimed in step (iii) of claim 1 , wherein catalytic hydrogenation is carried out in presence of Hand catalyst selected from the group consisting of Pd/C claim 1 , Pt/C claim 1 , Raney Ni claim 1 , Rh/C claim 1 , Platinum oxide claim 1 , Pd(OH)/C claim 1 , Lithium aluminium hydride claim 1 , ammonium formate or mixture thereof.6. The process as claimed in step (iii) of claim 1 , wherein the protecting groups are selected from the group consisting of Boc claim 1 , Cbz claim 1 , Tos or Fmoc preferably Boc.7. The process as claimed in step (v) of claim 1 , wherein temperature in the range of (−) 60 to (−) 90° C. preferably (−) 70 to (−) 80° C.8. The process as claimed in step (vi) of claim 1 , wherein acetylating agent used is selected from the group consisting of acetic anhydride claim 1 , acetyl chloride claim 1 , ...

Process for preparing n-h or n-alkyl 2-propynamide

Disclosed is a method for the synthesis of N—H or N-alkyl 2-propynamides useful as intermediate in the manufacture of pharmaceutically active ingredients.

Monomeric and Polymeric Linkers Useful For Conjugating Biological Molecules and Other Substances

The present invention concerns monomeric or polymeric linker molecules useful in biological and chemical applications, their synthesis, and the synthesis and use of derivatives of the linkers conjugated to a variety of detectable labels and other substances. The linkers may be used, for example, in conjunction with fluorescent labels, nucleic acid or nucleic acid analog probes, and solid phase systems, and to enhance the solubility of the conjugated molecules. 1. A linker synthesized from at least one di-carboxylic acid anhydride and at least one diamine wherein the diamine does not comprise more than two —CH2-CH2-O— groups.2. The linker of claim 1 , wherein the linker is an alternating co-polymer synthesized from the di-carboxylic acid anhydride and the diamine.35-. (canceled)6. A linker derivative comprising at least one linker of conjugated to at least one atom claim 1 , functional group claim 1 , or molecule.7. The linker derivative of claim 6 , wherein the at least one atom claim 6 , functional group claim 6 , or molecule comprises at least one detectable label or at least one probe.8. The linker derivative of claim 7 , wherein the at least one atom claim 7 , functional group claim 7 , or molecule comprises at least one detectable label claim 7 , and wherein the at least one detectable label comprises at least one color label.9. The linker derivative of claim 8 , wherein the at least one color label comprises at least one fluorophore.10. The linker derivative of claim 9 , comprising two or more fluorophores of the same or of different and distinguishable emission wavelengths.11. The linker derivative of claim 6 , comprising at least one nucleic acid or at least one nucleic acid analog.12. The linker derivative of claim 11 , wherein the at least one nucleic acid analog comprises PNA.13. The linker derivative of claim 6 , wherein the linker is further attached non-covalently or covalently to at least one solid surface.14. The linker derivative of claim 13 , ...

METHOD FOR PRODUCING ACRYLAMIDE AQUEOUS SOLUTION

There is provided a method for producing an aqueous acrylamide solution by producing acrylamide by reacting a composition including acrylonitrile with water, in which the composition including acrylonitrile includes 20 to 80 mg of methacrylonitrile per 1 kg of the total weight of the composition including acrylonitrile. According to the present invention, a production method allowing stable obtainment of an aqueous acrylamide solution can be provided as polymerization of the acrylamide can be suppressed without causing a decreas+455e in quality. 1. A method for producing an aqueous acrylamide solution , the method comprising reacting a composition comprising acrylonitrile with water to produce acrylamide ,wherein the composition comprises 20 to 80 mg of methacrylonitrile per 1 kg of a total weight of the composition.2. The method according to claim 1 , wherein the reacting of the composition with water is performed in the presence of a biocatalyst.3. The method for according to claim 1 , wherein the composition further comprises 2 to 20 mg of acetonitrile per 1 kg of the total weight of the composition.4. The method for according to claim 1 , wherein a concentration of the acrylamide in the aqueous acrylamide solution is from 30 to 60% by mass relative to a total mass of the aqueous acrylamide solution. The present invention relates to a method for producing an aqueous acrylamide solution.The present application claims priority to Japanese Patent Application No. 2011-112429, which has been filed in Japan on May 19, 2011, which is hereby incorporated by reference in its entirety.Acrylamide has many applications, such as flocculating agents, petroleum recovering agents, paper strength enhancers in the paper producing industry, and thickeners for papermaking, and is a useful substance as a raw material for polymers.Among industrial processes for acrylamide production, used long time ago is a sulfuric acid hydrolysis process which consists of the step of heating ...

METHOD FOR PREPARING 2-ARYL MALONAMIDE AND APPLICATIONS THEREOF

Disclosed are a method for preparing 2-aryl malonamide and an application thereof. This method uses 2-(cyclohexenylidene) malononitrile as a raw material, which undergoes an aromatization-hydrolyzation reaction in the presence of an oxidant and water to produce 2-aryl malonamide by one step. Compared to the prior art, the method for preparing 2-aryl malonamide of this application has the following features and advantages: (1) this method employs a completely different synthetic strategy; (2) raw materials used in this method are easily obtained; (3) this method not only has high yield, but also does not require expensive metal catalysts. This method is lower-cost, suitable for the industrial production. 2. The method of claim 1 , wherein Rand Reach are independently a C-Calkyl group or a C-Caryl group; Ris a C-Calkyl group; and Rand Reach are hydrogen.3. The method of claim 2 , wherein Rand Reach are ethyl claim 2 , and Ris methyl.4. The method of claim 1 , wherein the oxidant is peroxide claim 1 , oxygen claim 1 , air or an oxidizing acid; and a molar ratio of the oxidant to the compound 1 is 0.5-2.0:1.5. The method of claim 4 , wherein the oxidant is potassium persulfate or concentrated sulfuric acid; and the molar ratio of the oxidant to the compound 1 is 1.0-1.2:1.6. The method of claim 1 , wherein a temperature of the aromatization-hydrolyzation reaction is 0-100° C.7. The method of claim 6 , wherein the temperature of the aromatization-hydrolyzation reaction is 60-80° C.8. The method of claim 1 , wherein the aromatization-hydrolyzation reaction is carried out in the presence of an acid.9. The method of claim 8 , wherein the acid is concentrated sulfuric acid. This application is a continuation of International Patent Application No. PCT/CN2017/079686, filed on Apr. 7, 2017, which is incorporated herein by reference in its entirety.This application relates to organic synthesis, and specifically to a method for preparing 2-aryl malonamide and applications ...

Process for Preparing Lacosamide

The present invention provides a process for the preparation of lacosamide in substantially optically pure form, which in one aspect comprises the following steps: (i) resolution of O-methyl-D,L-serine to provide O-methyl-D-serine in substantially optically pure form; (ii) acetylation of O-methyl-D-serine thereby obtained to provide the N-acetyl 10 derivative thereof in substantially optically pure form; (iii) activating the carboxy group of the compound thereby obtained; and (iv) reacting the compound thereby obtained with benzylamine. 2. The process as claimed in wherein claim 1 , in part (ii) claim 1 , the acetylation reaction is effected by treating compound (III) with acetic anhydride in a mixture of tetrahydrofuran and water.3. The process as claimed in wherein the ratio of tetrahydrofuran to water is in the region of 6:1 parts by volume.4. The process as claimed in wherein Qrepresents isobutoxycarbonyloxy.5. The process as claimed in wherein claim 1 , in part (iv) claim 1 , the reaction between compound (V) and benzylamine is effected in tetrahydrofuran at a low temperature; followed by quenching with an acidic solution at a low temperature. The present invention relates to the preparation of a therapeutically active compound. More particularly, the invention concerns an improved process for manufacturing lacosamide.Lacosamide, i.e. (R)-2-acetylamino-N-benzyl-3-methoxypropionamide, has been approved for sale as a medicine by regulatory agencies throughout the world. By way of illustration, the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) have both approved lacosamide as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy.Various methods for preparing lacosamide are known from the prior art. For example, WO 2010/052011 describes a process for manufacturing substantially optically pure lacosamide comprising resolution of 2-acetamido-N-benzyl-3-methoxypropionamide, typically in ...

LIPIDS, LIPID COMPLEXES AND USE THEREOF

The present invention is related to uses of a composition comprising a pharmaceutically active component and a compound according to formula (I), 1. A method for the synthesis of N-palmityl-oleylamine comprising the following steps:providing oleic acid;providing palmitylamine;reacting the oleic acid and the palmitylamine to form N-palmityl-oleoylamide; andreducing the N-palmityl-oleoylamide to N-palmityl-oleylamine,whereby the oleic acid is at least 90% pure, whereby the percentage is the molar ratio of oleic acid and any fatty acid different from oleic acid.2. The method according to claim 1 , wherein the oleic acid and the palmitylamine are reacted at room temperature.3. The method according to claim 1 , wherein the oleic acid is subject to a pre-treatment prior to reacting it with the palmitylamine claim 1 , whereby the pre-treatment comprises reacting the oleic acid with ethylchloroformate.4. The method according to claim 1 , wherein the reaction is performed at 0° C.5. The method according to claim 3 , whereby the reaction is further reacted with an acid scavenger.6. The method according to claim 1 , whereby the molar ratio of chloroformic acid ethyl ester claim 1 , oleic acid claim 1 , triethylamine and palmitylamine is about 1-1.05:1:1:1-3:1-1.10.7. The method according to claim 1 , wherein the reduction of the N-palmityl-oleoylamide to N-palmity-oleylamine is performed using LiAlH.8. The method according to claim 1 , wherein upon reacting the oleic acid with the palmitylamine claim 1 , the reaction is washed claim 1 , precipitated and the precipitate thus obtained optionally re-crystallised.9. The method according to claim 5 , wherein the acid scavenger is selected from the group comprising triethylamine claim 5 , diisopropylethylamine and pyridine.10. The method according to claim 4 , wherein the reaction is performed at 0° C. under inert gas.11. The method according to claim 3 , wherein the oleic acid is reacted with ethylchloroformate in anhydrous ...

METHOD FOR PRODUCING AMIDE

A method for producing an amide includes: subjecting carboxylic acids to dehydration condensation or causing a reaction between a carboxylic acid and a haloformic acid ester; and subsequently causing a reaction with a first base and a reaction with an amine to obtain an amide, wherein the reaction with a first base and/or the reaction with an amine is performed by adding an acid thereto. 1. A method for producing an amide , the method comprising:subjecting carboxylic acids to dehydration condensation or causing a reaction between a carboxylic acid and a haloformic acid ester; andsubsequently causing a reaction with a first base and a reaction with an amine to obtain an amide,wherein the reaction with a first base and/or the reaction with an amine is performed by adding an acid thereto.2. The method for producing an amide , the method comprising:mixing a product obtained by reacting a mixture obtained by mixing a first carboxylic acid with a second carboxylic acid or a product obtained by reacting a mixture obtained by mixing a carboxylic acid and a haloformic acid ester, with a first base, an acid, and an amine.3. The method for producing an amide according to claim 1 ,wherein phosgene or a phosgene equivalent that decomposes in a reaction system and produces phosgene is caused to react, and the carboxylic acids are subjected to dehydration condensation.4. The method for producing an amide according to claim 1 ,wherein the same kinds of the carboxylic acids are subjected to dehydration condensation.5. The method for producing an amide according to claim 1 ,wherein the haloformic acid ester is any one or more kinds selected from the group consisting of isopropyl chloroformate, isobutyl chloroformate, ethyl chloroformate, isopropyl bromoformate, isobutyl bromoformate, and ethyl bromoformate.6. The method for producing an amide according to claim 1 , the method further comprising:causing a reaction between the haloformic acid ester and a second base that activates the ...

MICROFLUIDIC DEVICE FOR SERIAL FLUIDIC OPERATIONS

An integrated microfluidic device for carrying out a series of fluidic operations includes a housing including a plurality of n microfluidic conduits, wherein n is at least three, and a rotating valve having an internal channel with an entrance port and an exit port that are angularly separated. The rotating valve is positionable in a first position to connect two of the n fluidic conduits via the internal channel, and upon rotating the valve to a second position, two other of the n fluidic conduits are connected by the internal channel. The device further may include one or more fluidic chambers in fluid communication with respective fluidic conduits. Fluid contained in one fluidic chamber is transferrable by application of positive or negative gas pressure through associated fluidic conduits into another fluidic chamber via the internal channel. The device may be utilized to perform a variety of fluidic operations. 1. An integrated microfluidic device for carrying out a series of fluidic operations comprising:a housing including a plurality of n microfluidic conduits, wherein n is at least three; anda rotating valve having an internal channel with an entrance port and an exit port that are angularly separated;wherein the rotating valve is positionable in a first position to connect two of the n fluidic conduits via the internal channel, and upon rotating the valve to a second position, two of the n fluidic conduits, including at least one fluidic conduit different from the fluidic conduits connected in the first position, are connected by the internal channel; andwherein in either the first position or the second position, two sequentially adjacent fluidic conduits are connected via the internal channel.2. The integrated microfluidic device of claim 1 , wherein the two of the n fluidic conduits connected in the second position includes at least one of the fluidic conduits connected to the internal channel in the first position.3. The integrated microfluidic device ...

PREPARATION OF LIPOAMINO ACIDS AND LIPOPEPTIDES USING SALTS AS CO-REACTANTS

Methods for synthesizing a lipoamino acid and a lipopeptide are provided. The method can include reacting a fatty acid with an amino acid or a peptide and a co-reactant salt to form a lipoamino acid or a lipopeptide, respectively. The co-reactant salt is generally a magnesium sulfate, magnesium carbonate, potassium carbonate, iron (II) sulfide (troilite), or a mixture thereof. 1. A method of synthesizing a lipoamino acid , the method comprising:reacting a fatty acid with an amino acid and a co-reactant salt to form a lipoamino acid, wherein the co-reactant salt comprises magnesium sulfate, magnesium carbonate, potassium carbonate, iron (II) sulfide (troilite), or a mixture thereof.2. The method as in claim 1 , wherein the molar ratio of the amino acid to the fatty acid is about 0.5:1 to about 5:1.3. The method as in claim 1 , wherein the amino acid comprises alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glutamine claim 1 , glutamic acid claim 1 , glycine claim 1 , histidine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , serine claim 1 , threonine claim 1 , tryptophan claim 1 , tyrosine claim 1 , valine claim 1 , other alpha- or of beta- or gamma amino acids or mixtures thereof.4. The method as in claim 1 , wherein the fatty acid comprises a saturated fatty acid.5. The method as in claim 4 , wherein the saturated fatty acid comprises caprylic acid claim 4 , lauric acid claim 4 , tridecylic acid claim 4 , myristic acid claim 4 , pentadecylic acid claim 4 , cetylic acid claim 4 , heptadecanoic acid claim 4 , stearic acid claim 4 , arachidic acid claim 4 , behenic acid or mixtures thereof or of branched chain saturated fatty acid comprises straight chain fatty acids with one or more alkyl groups bonded to carbons at various locations along the length of the chain.6. The method as in claim 1 , wherein the fatty acid comprises an ...

AMIDE COMPOUND, PREPARATION METHOD AND USES THEREOF

Disclosed are amide compounds, preparation method and uses thereof, specifically, the compounds represented by formula I or pharmaceutically acceptable salts, wherein R, R, R, R, R, Q, X and n are defined as in the description. Also disclosed are a method for preparing the compounds of formula I, a composition containing the compounds, and the uses of the same in the preparation of medicaments for regulating blood lipid and/or preventing gallstone. The compounds of formula I disclosed in the present invention have stability in vitro, good solubility in the pharmaceutical organic solvents and favorable bioavailability in animals. 3. The compounds represented by formula I according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein:R1 is mono-substituted or poly-substituted phenyl, wherein the substituent on the phenyl is characterized by having at least one hydroxy substituent;R2 and R8 are independently select from mono-substituted or di-substituted phenyl, wherein the substituent on the phenyl is halogen, C1-C6 alkyl or C1-C6 alkoxy;R3, R4, R5, R6 and R7 are independently selected from H or substituted or non-substituted C1-C6 alkyl;Q is methylene;X is oxygen;m is an integer from 0 to 5; andn is an integer from 0 to 5;4. The compounds represented by formula I according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein R1 is p-hydroxyphenyl.5. The compounds represented by formula I according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein R2 and R8 are 2 claim 1 ,5-dimethylphenyl.6. The compounds represented by formula I according to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein R3 claim 1 , R4 claim 1 , R6 and R7 are methyl.7. The compounds represented by formula I according to any one of the to claim 1 , or pharmaceutically acceptable salts thereof claim 1 , wherein both m and n are 3.8. The compounds represented by formula I according to claim 1 , or ...

SYNTHESIS OF DIAMIDO GELLANTS BY USING DANE SALTS OF AMINO ACIDS

The invention relates to a method for the synthesis of a compound according to formula I comprising the following steps: a) reacting a Dane salt according to formula II and a Dane salt according to formula III with a coupling reagent; b) adding a diamine according to formula IV to the reaction mixture; and c) adding an acid to the reaction mixture to adjust the pH value of the reaction to <7; wherein L represents a C-Calkyl group, a C-Caryl group, or a C-Calkylaryl group; Rand Rcan be identical or different and represent a hydrogen atom, a C-Calkyl group, a C-Chydroxyalkyl group, a C-Cthioether group, a C-Caryl group, a C-C) alkylaryl group, a C-Calkylhydroxyaryl group, a C-Calkylheteroaryl group with 1 to 4 heteroatoms; or a C-Calkylcarboxylic moiety, which may be an acid, an amide, or which may be esterified with a C-Calkyl group or a C-Calkylaryl group; Rrepresents a C-Calkyl group; Rrepresents a hydrogen atom, or a C-Calkyl group; Rrepresents a C-Calkyl group; and X represents an alkali metal. 2. Method according to claim 1 , wherein Rand Rcan be identical or different and represent a hydrogen atom claim 1 , a n-butyl group claim 1 , a t-butyl group claim 1 , a propyl group claim 1 , a cyclopropyl group claim 1 , an ethyl group claim 1 , or one of the side chains of the amino acids alanine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , methionine claim 1 , phenylalanine claim 1 , tyrosine claim 1 , tryptophan claim 1 , serine claim 1 , threonine claim 1 , glutamine claim 1 , asparagine claim 1 , esters of glutamic acid claim 1 , or esters of aspartic acid.3. Method according to claim 1 , wherein L represents a C-Clinear alkyl group claim 1 , a 1 claim 1 ,4-dimethylcyclohexyl group claim 1 , or a xylene group.4. Method according to claim 1 , wherein Rrepresents a methyl group.5. Method according to claim 1 , wherein Rrepresents a hydrogen atom.6. Method according to claim 1 , wherein Rrepresents a methyl or ethyl group.7. Method according to ...

AMIDES, USE OF AMIDES AS SOLVENTS FOR ORGANIC COMPOUNDS, COMPOSITIONS AND EMULSIONS CONTAINING AMIDES, AND METHOD FOR TREATING A PLANT

The present invention relates in general to the use of amides of the following general formula (I) wherein Ris a linear or branched hydrocarbyl group containing 9 to 14 carbon atoms; Ris selected from the group consisting of methyl, ethyl and benzyl; and Ris selected from the group consisting of hydrogen, methyl and ethyl, as solvents for organic agriculturally active ingredients, compositions comprising organic agriculturally active ingredients and such amides, methods for treating a plant utilizing such compositions, as well as some of the amides as such and methods for their production. 2. The amide according to claim 1 , wherein Ris methyl or hydrogen.3. The amide according to claim 2 , wherein Ris methyl. The present invention relates to the use of certain amides as solvents for organic compounds, and to compositions comprising organic agriculturally active ingredients dissolved in the amides. Further, the present invention relates to methods for treating a plant utilizing compositions of the present invention. In addition, the present invention relates to certain amides as such as well as methods for their production.Organic solvents are commonly used for dissolving organic compounds being water insoluble or having low water solubility. Many agriculturally active ingredients, such as pesticide and plant growth regulators, are organic compounds that commonly are water insoluble, or have low water solubility. Hence, solvents have typically been used in the preparation of agricultural formulations, in order to prepare aqueous agricultural formulations with a concentration of agricultural actives exceeding the solubility thereof in water.Agricultural formulations are conventionally provided in the form of concentrated compositions, which are diluted with water by the end-user to obtain the work-composition that is eventually used, e.g. sprayed on a crop field. In the case of e.g. water-insoluble agricultural actives, the concentrated composition may be a so-called ...

MECHANOCHEMICAL SYNTHESIS OF RADIOGRAPHIC AGENTS INTERMEDIATES

The present invention generally relates to a process using a mechanochemical approach exploiting the mechanical milling of reactants for the manufacturing of acetyl Iopamidol and, more generally, of key intermediates of radiographic contrast agents, and of the contrast agents themselves. 2) The process according to wherein serinol and compound (II) are used at a molar ratio of from 2 to less than 6.3) The process according to wherein the mechanical co-milling of compound (II) and serinol is carried out in the presence of a base.4) The process according to wherein the base is an organic base selected from Triethanolamine and N-methylmorfoline.5) The process according to carried out by using from 2 to 5 moles of serinol for each mole of compound (II).6) The process according to wherein compound (II) and serinol are used at a molar ratio of from 1:2 to 1:3.7) The process according to wherein compound (II) and base are used at a molar ratio of from 1:3 to 1:10.8) The process according to claim 1 , wherein the milling is carried out at a rotation speed of from 400 to 1000 rpm.9) The process according to wherein the process is carried out at a reaction time of from 20 to 180 min.10) The process according to carried out in the presence of a volume of a lubricant ranging from 0.5 to 1.5 the amount claim 1 , by weight claim 1 , of compound (II).11) (canceled)12) A process for the preparation of Iopamidol which comprises:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) obtaining Acetyl Iopamidol by mechanical, milling of compound (I) and serinol by use of the process according to ;'}b) converting the Acetyl Iopamidol into Iopamidol by hydrolysis of an acetyl group and purification of the Iopamidol.14. The process according to wherein in the compound of formula (V):{'sub': 1', '1', '3, 'Ris a C-Calkyl substituted by 1 or 2 hydroxyl groups{'sub': '2', 'Ris H, and'}{'sub': '3', 'claim-text': {'sub': 3', '1', '3', '3, 'Ris a C-Calkyl optionally substituted by one or more ...

PROCESS FOR PREPARATION OF MIDODRINE AND INTERMEDIATES THEREOF

The invention relates to process for the preparation of midodrine or pharmaceutically acceptable salts thereof. The invention also relates to process for the preparation of intermediates of midodrine. 2. The process according to claim 1 , wherein the reaction at step (a) is performed in the presence of a Lewis acid selected from AlCl claim 1 , AlBr claim 1 , FeCl claim 1 , and FeBr.3. The process according to claim 1 , wherein the reaction at step (b) is performed using potassium phthalimide or sodium phthalimide.4. The process according to claim 1 , wherein the conversion of the compound of Formula (V) into the compound of Formula (IV) at step (c) is performed in the presence of a base or an acid.5. The process according to claim 4 , wherein the base is selected from sodium hydroxide claim 4 , potassium hydroxide claim 4 , lithium hydroxide claim 4 , sodium carbonate claim 4 , potassium carbonate claim 4 , caesium carbonate claim 4 , methylamine claim 4 , ethylamine claim 4 , dimethylamine claim 4 , diethylamine claim 4 , methylethylamine claim 4 , triethylamine claim 4 , ammonium hydroxide claim 4 , and hydrazine hydrate.6. The process according to claim 4 , wherein the acid is selected from hydrochloric acid claim 4 , hydrobromic acid claim 4 , acetic acid claim 4 , trichloroacetic acid claim 4 , and trifluoroacetic acid.7. The process according to claim 1 , wherein the conversion of the compound of Formula (IV) into the compound of Formula (III) at step (c) is performed in the presence of a reducing agent selected from lithium aluminium hydride claim 1 , lithium borohydride claim 1 , sodium borohydride claim 1 , zinc borohydride claim 1 , calcium borohydride claim 1 , sodium cyanoborohydride claim 1 , diisobutylaluminium hydride claim 1 , L-selectride claim 1 , diborane claim 1 , diazene claim 1 , aluminum hydride claim 1 , Red-Al claim 1 , and sodium triacetoxyborohydride.8. The process according to claim 1 , wherein the conversion of the compound of Formula ( ...

METHOD FOR SYNTHESIZING TETRAALKYLNITRILOACETIC ACID DIACETAMIDE COMPOUND

In synthesis of a compound represented by the General Formula (1) or a salt thereof, nitrilotriacetic acid as its raw material is reacted with a dehydrating agent to allow dehydration, and the resulting nitrilotriacetic acid anhydride is reacted with a dialkylamine to obtain a reaction intermediate product. The reaction intermediate product is then similarly reacted with a dehydrating agent to allow dehydration, and the resulting reaction intermediate anhydride is reacted with a dialkylamine to synthesize a tetraalkylnitriloacetic acid diacetamide compound. 2. The method according to claim 1 , wherein the dehydrating claim 1 , agent used in Step (I) and Step (II) is selected from the group consisting of acetic anhydride claim 1 , trichloroacetic anhydride claim 1 , trifluoroacetic anhydride claim 1 , and a mixture thereof.3. The method according to claim 1 , wherein in Step (I) and Step (II) dehydration is performed by reacting 2 to 6 equivalents of a dehydrating agent with the nitrilotriacetic acid (i) and/or the nitrilotriacetic acid derivative (iii).4. The method according to claim 1 , wherein in Step (I) and Step (II) claim 1 , after the dehydration of nitrilotriacetic acid (i) and/or the nitrilotriacetic acid derivative (iii) claim 1 , an operation of evaporation of unreacted dehydrating agent under reduced pressure is performed.5. The method according to claim 1 , wherein in Step (I) and Step (II) claim 1 , a solvent used for the dehydration reaction of in nitrilotriacetic acid (i) and/or the nitrilotriacetic acid derivative (iii) is selected from the group consisting of pyridine claim 1 , dimethylformamide claim 1 , dimethylacetamide claim 1 , and a mixture thereof.6. The method according to claim 1 , wherein in Step (I) and Step (II) claim 1 , 1.0 to 1.1 equivalents of the dialkylamine is reacted with the nitrilotriacetic acid anhydride (ii) and/or the nitrilotriacetic acid derivative anhydride (iv).8. The method according to claim 1 , wherein the compound ...

PROCESSES FOR THE SYNTHESIS OF 2-AMINO-4,6-DIMETHOXYBENZAMIDE AND OTHER BENZAMIDE COMPOUNDS

This invention provides a method for the synthesis of a 2-amino-4,6-dimethoxybenzamide and other benzamides of Compound I: wherein R, R, R, and Reach independently represent a hydrogen, a C-Calkyl, or a C-Calkoxy; and wherein Rand Reach independently represent a hydrogen, a C-Calkyl, a protecting group, or a directing group. 3. The process according to wherein prior to step (iv) claim 2 , the at least one Compound IV is combined with at least one second precipitating agent to precipitate the at least one Compound IV.4. The process according to wherein prior to step (ii) claim 2 , the at least one Compound III is combined with at least one deprotecting agent such that the protecting group or directing group represented by Ris replaced with a hydrogen or a C-Calkyl.5. The process according to wherein prior to step (iii) claim 2 , the at least one Compound IV is combined with at least one deprotecting agent such that the protecting group or directing group represented by Ris replaced with a hydrogen or a C-Calkyl.7. The process according to wherein X represents Cl claim 2 , Br claim 2 , I claim 2 , —OTf claim 2 , —OMs claim 2 , or —OTs.8. The process according to wherein at least one of R claim 2 , R claim 2 , R claim 2 , R claim 2 , or Rrepresents a C-Calkoxy.9. The process according to wherein at least two of R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Reach independently represent a C-Calkoxy.10. The process according to wherein at least three of R claim 2 , R claim 2 , R claim 2 , R claim 2 , and Reach independently represent a C-Calkoxy.11. The process according to wherein Rand Reach independently represent a C-Calkoxy claim 2 , and Rand Reach represent a hydrogen.12. The process according to wherein the C-Calkoxy is a methoxy.13. The process according to claim 6 , wherein the protecting agent comprises an anhydride.14. The process according to claim 13 , wherein the anhydride is trifluoroacetic anhydride.15. The process according claim 2 , wherein the at ...

PROCESS OF MANUFACTURING AN ELECTRON TRANSPORT MATERIAL

A process of dissolving 3. The process of claim 1 , R are selected from the group consisting of: H claim 1 , CH claim 1 , carbonate claim 1 , SH claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , OH claim 1 , Si claim 1 , NH claim 1 , substituted alkyl chains and unsubstituted alkyl chains.4. The process of claim 1 , wherein the solvent is an organic solvent.5. 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 , ethanol claim 1 , hexane claim 1 , cyclohexane claim 1 , tetrahydrofuran and isopropanol.7. The process of claim 1 , wherein the reagent is a metal oxide.8. The process of claim 1 , wherein the reagent is selected from the group consisting of: dibutyltin (IV) oxide claim 1 , hydrochloric acid claim 1 , sulfuric acid claim 1 , nitric acid claim 1 , acetic acid and combinations thereof.9. The process of claim 1 , wherein R′ is —(CH)— claim 1 , wherein n is any integer of one or greater.10. The process of claim 1 , wherein R″ are selected from the group consisting of: N claim 1 , O claim 1 , S claim 1 , C claim 1 , B claim 1 , unsubstituted alkyl chains and substituted alkyl chains.11. The process of claim 9 , wherein the substitutions for the substituted alkyl chains are selected from the group consisting of: halogens claim 9 , NH claim 9 , Br claim 9 , OH claim 9 , Si claim 9 , S and combinations thereof.14. A process comprising:{'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 ethylenediamine to the second mixture to produce a third mixture; and{'sub': '60', 'd) refluxing the third mixture to ...

Amorphous Amides

An amorphous amide compound of the formula 2. The compound of claim 1 , wherein R is an alkyl group having from about 1 to about 22 carbon atoms.3. The compound of claim 1 , wherein R is an alkyl group having from about 2 to about 18 carbon atoms.8. The compound of claim 7 , wherein Ris an alkylene group having from about 1 to about 22 carbon atoms.12. The method of claim 11 , further comprising a catalyst.13. The method of claim 11 , wherein heating comprises heating to a temperature of from about 160 to about 180° C.14. The method of claim 11 , further comprising applying a vacuum pressure of from about 1 to about 2 millimeters of mercury for a period of from about 1 minute to about 1 hour.17. The method of claim 16 , further comprising a catalyst.18. The method of claim 16 , wherein heating comprises heating to a temperature of from about 160° C. to about 180° C.19. The method of claim 16 , further comprising applying a vacuum pressure of from about 1 to about 2 millimeters of mercury for a period of from about 1 minute to about 1 hour. Commonly assigned U.S. patent application Ser. No. ______ (Attorney Docket Number 20120800-US-NP), entitled “Phase Change Ink Containing Amorphous Amides,” having the named inventors Naveen Chopra, Adela Goredema, Kentaro Morimitsu, Barkev Keoshkerian, Jennifer L. Belelie, and Gabriel Iftime, filed concurrently herewith, is hereby incorporated by reference herein in its entirety.Commonly assigned U.S. patent application Ser. No. ______ (Attorney Docket Number 20120802-417885), entitled “Novel Crystalline Compounds for Phase Change Inks,” having the named inventors Adela Goredema, Jennifer Belelie, James Mayo, Daryl Vanbesien, Barkev Keoshkerian, Nathan Bamsey, and Jenny Eliyahu, filed concurrently herewith, is hereby incorporated by reference herein in its entirety.Commonly assigned U.S. patent application Ser. No. ______ (Attorney Docket Number 20120581-412786), entitled “Bio-renewable Phase Change Inks,” having the named ...

Method for producing beta-alkoxypropionamide

A method for producing a β-alkoxypropionamide including reacting a β-alkoxypropionic acid ester represented by the following formula (1) and an amine represented by the following formula (2) in the presence of a polyol and a basic catalyst, thereby to produce a β-alkoxypropionamide represented by the following formula (3), wherein, as the polyol, a reaction residue that is generated by the reaction and contains a used polyol is used: (wherein in the formulas, R and R′ are independently a C 1 to C 6 linear, branched or cyclic, saturated hydrocarbon group; R 1 and R 2 are independently a C 1 to C 6 linear, branched or cyclic, saturated hydrocarbon group; and R 3 is H or CH 3 ).

Synthesis of N1,N3-BIS(2,3-DIHYDROXYPROPYL)-5-NITROISOPHTHALAMIDE

The present disclosure generally relates to a new process for the preparation of high purity 5-nitro-isophthalamide compounds, which are useful as intermediates for the preparation of imaging agents, such as iodinated x-ray contrast imaging agents like ioversol, iohexyl and iopamidol. 2. The process of claim 1 , wherein R is selected from 2-hydroxyethyl claim 1 , 2 claim 1 ,3-dihydroxypropyl claim 1 , 3-hydroxypropyl claim 1 , 3 claim 1 ,4-dihydroxybutyl claim 1 , 4-hydroxybutyl and 1 claim 1 ,3-dihydroxy isopropyl.3. The process of claim 1 , wherein Rand Rare independently selected from methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , i-propyl claim 1 , n-butyl claim 1 , i-butyl and t-butyl.4. The process of claim 1 , wherein the solvent comprises methanol claim 1 , ethanol claim 1 , 1-propanol claim 1 , 2-propanol claim 1 , 1-butanol claim 1 , 2-butanol claim 1 , 2-methoxymethanol claim 1 , 2-ethoxyethanol claim 1 , 3-methoxypropanol claim 1 , formamide claim 1 , N-methylformamide claim 1 , or combinations thereof.5. The process of claim 1 , wherein the basic catalyst is a salt of an alkali metal and an alkoxide or an alkaline earth metal and an alkoxide.6. The process of claim 5 , wherein the metal is selected from sodium claim 5 , potassium claim 5 , lithium and magnesium claim 5 , and the alkoxide is selected from methoxide claim 5 , ethoxide claim 5 , i-propoxide claim 5 , t-butoxide and amoxide.7. The process of claim 1 , wherein the molar ratio of the primary amine to the diester is from 2:1 to about 2.4:1 claim 1 , from about 2.1:1 to about 2.2:1 claim 1 , from about 2.1:1 to about 2.3:1 claim 1 , or between about 2:1 and about 2.1:1.8. The process of claim 1 , wherein the molar ratio of the catalyst claim 1 , on an equivalent basis claim 1 , to the diester is from about 0.03:1 to about 0.1:1 claim 1 , from about 0.04:1 to about 0.1:1 claim 1 , from about 0.05:1 to about 0.09:1 claim 1 , or from about 0.06:1 to about 0.08:1.9. The process of claim 1 , ...

METHOD FOR PRODUCING N-BENZYL-2-BROMO-3-METHOXYPROPIONAMIDE AND INTERMEDIATES THEREOF

The present invention provides an industrially-preferable method for safely producing N-benzyl-2-bromo-3-methoxypropionamide at a high yield but at low cost. The method for producing of the present invention includes: in sequence, an amidation process that causes diacrylic anhydride to react with benzylamine in a solvent to obtain N-benzylacrylamide; a bromination process that causes N-benzylacrylamide to react with bromine in a solvent to obtain N-benzyl-2,3-dibromopropionamide; and a methoxylation process that causes N-benzyl-2,3-dibromopropionamide to react with methanol in the presence of a base to obtain N-benzyl-2-bromo-3-methoxypropionamide. 1. A method for producing N-benzyl-2-bromo-3-methoxypropionamide comprising:in sequence,an amidation process that causes diacrylic anhydride to react with benzylamine in a solvent to obtain N-benzylacrylamide;a bromination process that causes N-benzylacrylamide to react with bromine in a solvent to obtain N-benzyl-2,3-dibromopropionamide; anda methoxylation process that causes N-benzyl-2,3-dibromopropionamide to react with methanol in the presence of a base to obtain N-benzyl-2-bromo-3-methoxypropionamide.2. The method according to claim 1 , wherein diacrylic anhydride used in the amidation process is obtained by causing acrylic acid to react with a condensation agent in a solvent.3. The method according to claim 1 , wherein the solvent used in the amidation process is a mixture solvent of an organic solvent and water.4. The method according to claim 1 , wherein the solvent used in the amidation process contains a base.5. A method for producing N-benzyl-2 claim 1 ,3-dibromopropionamide comprising:in sequence,an amidation process that causes diacrylic anhydride to react with benzylamine in a solvent to obtain N-benzylacrylamide; anda bromination process that causes N-benzylacrylamide to react with bromine in a solvent to obtain N-benzyl-2,3-dibromopropionamide.6. The method according to claim 5 , wherein diacrylic ...

DCC Mediated Coupling for Halofenate Manufacture

The present application discloses a process for the preparation of a halofenate compound of the formula (III) or a salt thereof: 2. The process of claim 1 , wherein R is CalkylC(O)NHCalkyl or arylC(O)NHCalkyl claim 1 , X is F and X′ is Cl claim 1 , and the coupling agent is N claim 1 ,N′-dicyclohexylcarbodiimide.3. The process of claim 1 , wherein R is CHCONHCHCH— and X is F and X′ is Cl.4. The process of claim 1 , wherein the compound of formula (Ib) is N-acetylethanolamine.5. The process of any one of to claim 1 , wherein no base is used.7. The process of any one of to claim 1 , wherein the aprotic solvent is selected from the group consisting of toluene claim 1 , xylenes claim 1 , cyclohexane claim 1 , di-isopropyl ether claim 1 , isopropyl acetate claim 1 , THF claim 1 , hexanes and MTBE or combinations thereof.8. The process of claim 7 , wherein the aprotic solvent is toluene.9. The process of any one of to claim 7 , wherein the mole ratio of N claim 7 ,N′-dicyclohexylcarbodiimide to the compound of formula (Ia) is 1.05:1 to 1.15:1 claim 7 , and the mole ratio of the compound of formula (Ib) to the compound of formula (Ia) is 1.02:1 to 1.7:1.10. The process of claim 9 , wherein the mole ratio of N claim 9 ,N′-dicyclohexylcarbodiimide to the compound of formula (Ia) is 1.1:1 claim 9 , and the mole ratio of the compound of formula (Ib) to the compound of formula (Ia) is 1.5:1.11. The process of claim 10 , wherein the compound of formula (Ib) is N-acetylethanolamine.12. The process of any one of to claim 10 , wherein the process comprises:contacting a solution comprising N-acetylethanolamine in toluene with a solution of the compound of formula (Ia) in toluene;cooling the resulting solution at about 0° C.; andcontacting a solution of N,N′-dicyclohexylcarbodiimide in toluene with the solution comprising N-acetylethanolamine and the compound of formula (Ia) for a sufficient period of time to form the compound of formula (III).13. The process of claim 12 , further ...

PROCESS FOR THE PREPARATION OF 2-(TRIHALOMETHYL) BENZAMIDE

The present invention relates to a process for preparation of 2-(trihalomethyl) benzamide. 2. The process as claimed in claim 1 , wherein the reaction is carried out at a temperature in the range of about −75° C. to about 25° C.3. The process as claimed in claim 1 , wherein the reaction is carried out at a time period in the range of about 10 minutes to about 6 hours.4. The process as claimed in claim 1 , wherein the compound of Formula I is isolated by a process selected from the group consisting of filtration claim 1 , precipitation claim 1 , decantation claim 1 , crystallization claim 1 , evaporation claim 1 , layer separation and distillation or a combination thereof.5. The process as claimed in claim 1 , wherein the reaction mixture is stirred to facilitate the reaction. The present invention relates to a process for preparation of 2-(trihalomethyl) benzamide.The substituted benzamides, especially 2-(trihalo methyl) benzamide of Formula I, find vast usage in pharmaceutical and agrochemical field. The Welch et. al., (1969), 12(2), 299-303 describes a general process for preparation of α,α,α-trifluorotoluamides by reacting corresponding α,α,α-trifluorotoluic acid chloride with concentrated ammonium hydroxide. However, (1969), 12(2), 299-303 provides no specific example for such amidation reaction wherein the yield and purity of the product is illustrated.Despite the teaching of the prior art, the research for new preparation processes of halo alkyl substituted benzamides is still an active field and there still persists a need in the art to develop industrially scalable and economic process for the preparation of halo alkyl substituted benzamides.The main objective of the present invention is to provide a process for preparation of 2-(trihalomethyl) benzamide.An aspect of the present invention provides a process for the preparation of 2-(trihalomethyl) benzamide of Formula I,In an embodiment of the present invention, there is provided a process for the ...

CHEMICAL PROCESS FOR OPENING RING COMPOUNDS

It is described a process for the opening of lactone or lactam rings useful in the synthesis of pharmaceutically active compounds and the intermediates thereof, particularly Aliskiren. It has found that by selecting a type of solvent it is possible to obtain excellent yields and high optical and chemical purity of the isolated products. 121-. (canceled)22. An aminolysis process for the opening of a lactone or lactam ring , comprising the treatment of a compound containing said lactone or lactam ring with a primary or secondary amine in the presence of a catalyst and optionally of a cocatalyst , in a solvent in which the lactone or the lactam ring-containing compound is soluble and the amide produced in the reaction is insoluble in the reaction conditions , said primary or secondary amine having general formula RRNH , in which R and Rare , independently from each other , hydrogen or a group selected among a linear or branched C1-C6 alkyl , a linear or branched C1-C6 alkyl substituted with at least a substituent selected among a cyano group , a free carboxylic group , an ester , an amide , an aldehyde or an acetal , or an aryl (C1-C6) alkyl , with the condition that R and Rcannot be both hydrogen , and in which the amount of said amine is not higher than 3.5 equivalents compared to the molar quantity of the lactone or lactam ring-containing compound.24. The aminolysis process according to claim 22 , in which the amount of amine RR10NH is not lower than 1.5 equivalents compared to the molar quantity of the lactone or lactam ring-containing compound (II).25. The aminolysis process according to claim 22 , in which said catalyst is a Brønsted acid.26. The aminolysis process according to claim 25 , in which said acid is a carboxylic acid claim 25 , preferably monocarboxylic claim 25 , of general formula RCOH.27. The aminolysis process according to claim 26 , in which said group Ris a linear or branched alkyl claim 26 , a cycloalkyl claim 26 , a linear or branched alkenyl ...

SURFACE-MODIFIED NANODIAMOND, ORGANIC SOLVENT DISPERSION THEREOF, AND METHOD FOR PRODUCING SURFACE-MODIFIED NANODIAMOND

There are provided a surface-modified nanodiamond exhibiting easy dispersibility in an organic solvent, an organic solvent dispersion thereof, and a method for producing the surface-modified nanodiamond. The surface-modified nanodiamond according to the present invention includes a nanodiamond, and a group bound to a particulate surface of the nanodiamond and represented by formula (): 2. The surface-modified nanodiamond according to claim 1 , wherein the nanodiamond is a detonation nanodiamond or a high-temperature high-pressure nanodiamond.3. The surface-modified nanodiamond according to or claim 1 , wherein R in the formula (1) represents a straight-chain or branched-chain alkyl group having 1 to 22 carbon atoms or a 3- to 22-membered cycloalkyl group.4. An organic solvent dispersion of nanodiamonds claim 1 , being made by dispersing the surface-modified nanodiamond according to in an organic solvent.5. The organic solvent dispersion of nanodiamonds according to claim 4 , wherein the organic solvent has an SP value [(cal/cm): Fedors calculation value] at 25° C. of 7 to 23.6. The organic solvent dispersion of nanodiamonds according to or claim 4 , wherein the organic solvent has a relative permittivity at 25° C. of 1 to 40.8. The method for producing a surface-modified nanodiamond according to claim 7 , wherein the reaction of the nanodiamond with the nitrile compound represented by the formula (2) is carried out after a deagglutinating and/or crushing treatment for the nanodiamond or during a deagglutinating and/or crushing treatment for the nanodiamond. The present invention relates to a surface-modified nanodiamond, an organic solvent dispersion thereof, and a method for producing the surface-modified nanodiamond. The present application claims priority to Japanese Patent Application No. 2016-074518 and Japanese Patent Application No. 2016-074519, filed on Apr. 1, 2016 in Japan, the entire contents of which are hereby incorporated by reference.Nanodiamonds are ...

Method to Produce N-Acyl Amino Acid Surfactants Using N-Acyl Amino Acid Surfactants or the Corresponding Anhydrides as Catalysts

A process of producing N-acyl amino acid based surfactants of Formula I, 2. The process as claimed in claim 1 , wherein the catalytic amount of compounds of Formula I and Formula II claim 1 , is 0.05 to 0.5% by weight based on fatty acid.3. The process as claimed in claim 1 , wherein the amino acids used in the synthesis of compounds of Formula I are selected from naturally occurring α-amino acids.4. The process as claimed in claim 1 , wherein the naturally occurring α-amino acids are selected from Glycine claim 1 , Alanine claim 1 , Valine claim 1 , Leucine claim 1 , Isoleucine claim 1 , Methionine claim 1 , Proline claim 1 , Cystein claim 1 , Phenyl alanine claim 1 , Tyrosine claim 1 , Tryptophan claim 1 , Arginine claim 1 , Lysine claim 1 , Histidine claim 1 , Aspartic acid claim 1 , Glutamic acid claim 1 , Serine claim 1 , Threonine claim 1 , Aspergine and Glutamine.5. The process as claimed in claims 1 , wherein the amino acids used in the synthesis of compounds of Formula I are selected from unnatural amino acids and mixtures of stereoisomers.6. The process as claimed in claim 1 , wherein the unnatural amino acids are selected from amino propionic acid claim 1 , N-methyl taurine and Sarcosine.7. The process as claimed in claim 1 , wherein halogenations of fatty acids with thionyl chloride are carried out at 20 to 45° C.8. The process as claimed in claim 3 , wherein the naturally occurring α-amino acids are selected from Glycine claim 3 , Alanine claim 3 , Valine claim 3 , Leucine claim 3 , Isoleucine claim 3 , Methionine claim 3 , Proline claim 3 , Cystein claim 3 , Phenyl alanine claim 3 , Tyrosine claim 3 , Tryptophan claim 3 , Arginine claim 3 , Lysine claim 3 , Histidine claim 3 , Aspartic acid claim 3 , Glutamic acid claim 3 , Serine claim 3 , Threonine claim 3 , Aspergine and Glutamine.9. The process as claimed in claim 5 , wherein the unnatural amino acids are selected from amino propionic acid claim 5 , N-methyl taurine and Sarcosine. The present ...

METHOD FOR PRODUCING AMIDE COMPOUND

Provided is a novel method for producing amide compounds at high stereochemical selectivities. The method according to the present invention for producing amide compounds is provided with an amidation step for reacting, in the presence of a catalyst comprising a metal compound, an amino compound with an aminoester compound represented by general formula (1) to amidate the ester group in the aminoester compound. 2. The method for producing an amide compound according to claim 1 , further comprising a deprotection step wherein after the amidation step claim 1 , in the obtained amide compound claim 1 , the protecting group PG derived from the aminoester compound represented by general formula (1) is deprotected to obtain a converted amino group.3. The method for producing an amide compound according to claim 1 , further comprising an amidation step for reacting claim 1 , in the presence of a catalyst comprising a metal compound claim 1 , an amide compound having the amino group obtained in with an aminoester compound represented by general formula (1) to amidate the ester group of the aminoester compound.4. The method for producing an amide compound according to claim 1 , wherein the group PG is a tert-butoxycarbonyl group (Boc) claim 1 , benzyl group (Bn) claim 1 , benzyloxycarbonyl group (Cbz) claim 1 , benzoyl group (Bz) claim 1 , 2 claim 1 ,2 claim 1 ,2-trichloroethoxycarbonyl group (Troc) claim 1 , allyloxycarbonyl group (Alloc) claim 1 , 2 claim 1 ,4-dinitrophenyl group (2 claim 1 ,4-DNP) claim 1 , phthaloyl group (Phth) claim 1 , paramethoxy benzoyl group (PMPCO) claim 1 , cinnamoyl group claim 1 , toluene sulfonyl group (Ts) claim 1 , 2- or 4-nitrobenzene sulfonyl group (Ns) claim 1 , or 9-fluorenyl methyloxycarbonyl group (Fmoc).6. The method for producing an amide compound according to claim 1 , wherein the amino compound is an amino acid or a salt thereof claim 1 , or an amino acid ester or a salt thereof.7. The method for producing an amide compound ...

METHOD FOR PRODUCING A-HYDROXYISOBUTYRIC ACID AMIDE AND REACTOR

The present invention provides a method for producing α-hydroxyisobutyric acid amide by hydration of acetone cyanohydrin under the presence of a catalyst composed mainly of manganese oxide using a reactor in which at least two reaction regions are connected in series, the method being characterized by comprising: a step (B) of cyclically supplying at least a portion of a reaction liquid withdrawn from at least one reaction region to a first reaction region (I) in the reactor; and a step (b1) of further cyclically supplying at least a portion of the reaction liquid withdrawn from at least one reaction region to at least one reaction region other than the first reaction region. The method is also characterized in that an oxidizing agent is supplied to at least one reaction region in the reactor.

PROCESS FOR PREPARING 2,2-DIBROMOMALONAMIDE

The present invention generally relates to a process for preparing 2,2-dibromomalonamide from 2,2-dibromo-3-cyanoacetamide. 1. A process for converting a first biocidal formulation to a second biocidal formulation , the process comprising providing a first biocidal formulation comprising a first amount of 2 ,2-dibromo-3-cyanoacetamide and water , contacting together the first biocidal formulation and an effective amount of a nitrile-amide-conversion composition to form a reaction mixture comprising a second biocidal formulation , the second biocidal formulation comprising water and 2 ,2-dibromomalonamide , the contacting being performed in such a way so as to produce the second biocidal formulation , and wherein the process further comprisesa. obtaining a mother liquor from the reaction mixture;b. preparing another nitrile-amide-conversion composition comprising most of the mother liquor;c. contacting the other nitrile-amide-conversion comprising the mother liquor to another amount of 2,2-dibromo-3-cyanoacetamide to form another reaction mixture, the contacting the other nitrile-amide-conversion comprising the mother liquor to another amount of 2,2-dibromo-3-cyanoacetamide being performed in such a way so as to produce additional 2,2-dibromomalonamide.2. The process as in claim 1 , the second biocidal formulation further comprising at least one other biocidal formulation ingredient.3. The process as in claim 2 , the at least one other biocidal formulation ingredient comprising hydrogen peroxide claim 2 , an unreacted portion of the amount of 2 claim 2 ,2-dibromo-3-cyanoacetamide claim 2 , or a combination thereof.4. The process as in claim 2 , the process further comprising maintaining pH of the reaction mixture during the contacting step at less than pH 9.0.5. The process as in claim 4 , the process further comprising maintaining pH of the reaction mixture during the contacting step at a pH from pH 4.0 to less than pH 9.0.6. The process as in claim 5 , the process ...

BENDAMUSTINE DERIVATIVES AND RELATED COMPOUNDS, AND MEDICAL USE THEREOF IN CANCER THERAPY

The present invention relates to bendamustine derivatives and related compounds of formula (VII), (VIII) and (IX), and medical uses thereof in particular in cancer therapy. 115.-. (canceled)17. The compound of formula IX according to claim 16 , wherein the compound is in the form of a salt claim 16 , and particularly in the form of a hydrate.18. The compound of formula IX according to claim 17 , wherein the salt comprises 0.6 to 1.4 mol water relative to 1 mol of the compound claim 17 , and particularly 0.8 to 1.2 mol water relative to 1 mol of the compound.19. The compound of formula IX according to claim 16 , wherein the compound is in the form of a base addition salt in which the base is selected from the group consisting of magnesium hydroxide claim 16 , calcium hydroxide claim 16 , zinc hydroxide claim 16 , potassium hydroxide claim 16 , sodium hydroxide claim 16 , potassium carbonate claim 16 , sodium carbonate claim 16 , potassium hydrogen carbonate claim 16 , sodium hydrogen carbonate claim 16 , diethylamine claim 16 , triethylamine claim 16 , ethanolamine (2-aminoethanol) claim 16 , diethanolamine (2 claim 16 ,2′-iminobis(ethanol)) claim 16 , triethanolamine (2 claim 16 ,2′ claim 16 ,2″-nitrilotris(ethanol)) claim 16 , ethylenediamine claim 16 , piperazine claim 16 , piperidine claim 16 , pyrrolidine claim 16 , pyridine claim 16 , morpholine claim 16 , 1H-imidazole claim 16 , N-methyl-glucamine claim 16 , L-lysine claim 16 , choline claim 16 , L-arginine claim 16 , benethamine claim 16 , 4-(2-hydroxyethyl)morpholine claim 16 , tromethamine claim 16 , 2-(dimethylamino) ethanol (Deanol) claim 16 , 1-(2-hydroxyethyl)pyrrolidine claim 16 , 2-(diethylamino)-ethanol claim 16 , benzathine claim 16 , hydrabamine claim 16 , and betaine.20. The compound of formula IX according to claim 16 , wherein:{'sub': 1', '2', '1', '2', '1', '2', '1', '2, '(A) Ris C1-C6 alkyl, Ris C1-C6 alkanediyl, and Yand Yrepresent oxygen; and particularly Ris C1-C4 alkyl, Ris C1-C4 ...

PROCESSES FOR PRODUCING HEXANEDIOL (HDO), HEXAMETHYLENEDIAMINE (HMD), ADIPONITRILE (ADN), ADIPAMIDE (ADM) AND DERIVATIVES THEREOF

Processes include producing hexanediol (HDO), hexamethylenediamine (HMD), adiponitrile (ADN), adipamide (ADM) and derivatives thereof from fermentation broths containing diammonium adipate (DAA), monoammonium adipate (MAA) and/or adipic acid (AA). 1. A process for producing nitrogen-containing compounds comprising:(a) providing a clarified DAA-containing fermentation broth;(b) distilling the broth to form an overhead that comprises water and ammonia, and a liquid bottoms that comprises MAA, at least some DAA, and at least about 20 wt % water;(c) cooling and/or evaporating the bottoms, and optionally adding an antisolvent to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing solid portion that is substantially free of DAA;(d) separating the solid portion from the liquid portion;(e) recovering the solid portion;(f) contacting at least a part of the solid portion at least one hydrogenation catalyst to produce HDO;(g) aminating HDO to produce HMD; and(h) recovering the HMD.2. A process for making nitrogen-containing compounds comprising:(a) providing a DAA-containing fermentation broth;(b) distilling the broth to form a first overhead that comprises water and ammonia, and a first liquid bottoms that comprises MAA, at least some DAA, and at least about 20 wt % water;(c) cooling and/or evaporating the bottoms, and optionally adding an antisolvent to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing solid portion that is substantially free of DAA;(d) separating the solid portion from the liquid portion;(e) recovering the solid portion;(f) dissolving the solid portion in water to produce an aqueous MAA solution;(g) distilling the aqueous MAA solution at a temperature and pressure sufficient to form a second overhead that comprises water and ammonia, and a second ...

PROCESS FOR PREPARING N-ACYL AMINO ACID SALTS

N-Acyl amino acid salt compositions and an improved process for making them from fatty alkyl esters are disclosed. The process comprises reacting a fatty alkyl ester with an amino acid salt in the presence of an alkoxide catalyst at a pressure of at least 5 psig. At least 1 0 mole percent of catalyst is used based on the amount of fatty alkyl ester used as a reactant. Pressure and a minimum level of alkoxide catalyst are needed to give high fatty alkyl ester conversions and good yields of the desired N-acyl amino acid salt. The resulting N-acyl amino acid salt compositions have low color, an acceptable level of fatty acid soaps, and a small proportion of di-acylated by-products. Single-phase mixtures produced by combining various amino acid salts with glycinates, or by using an excess of either the fatty alkyl ester or amino acid salt, promote high conversions when the mixtures are reacted to give the desired N-acyl amino acid salt. 1. A process which comprises reacting a fatty alkyl ester with an amino acid salt in the presence of at least 10 mole % , based on the amount of fatty alkyl ester , of an alkoxide catalyst at a pressure of at least 5 psig to produce a composition comprising an N-acyl amino acid salt.2. The process of wherein the catalyst comprises a C-Calkoxide.3. The process of wherein the catalyst is sodium methoxide/methanol.4. The process of wherein the catalyst is used in an amount within the range of 12 to 50 mole %.5. The process of wherein the reaction is performed at a pressure within the range of 5 psig to 50 psig.6. The process of wherein the fatty alkyl ester is a C-Cmethyl ester.7. The process of wherein the amino acid salt is an alkali metal salt of an amino acid selected from the group consisting of glycine claim 1 , alanine claim 1 , glutamine claim 1 , glutamic acid claim 1 , and aspartic acid.8. The process of wherein the amino acid salt is an alkali metal salt of glycine.9. The process of wherein the reaction is performed in the ...

METHOD FOR PREPARING 2-AMINO-N-(2,2,2-TRIFLUOROETHYL) ACETAMIDE

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. 2. The method of step (A) wherein the compounds of Formulae 2 and 3 and the coupling reagent are contacted in the presence of a base and a water immiscible solvent.3. The method of wherein the base is derived from the coupling reagent and the coupling reagent is N claim 2 ,N′-carbonyldiimidazole.4. The method of step (B) wherein the compound of Formulae 4 and hydrogen are contacted in the presence of a hydrogenolysis catalyst and a water immiscible solvent.5. The method of wherein the hydrogenolysis catalyst is palladium on carbon.6. The method of step (C) wherein the compound claim 1 , of Formula 1 is contacted with an acid of Formula 5 in the presence of a water immiscible solvent.7. The method of wherein the acid of Formula 5 comprises hydrogen chloride.89-. (canceled)11. The method of step (A1) wherein the compounds of Formulae 8 and 3 and the coupling reagent are contacted in the presence of a base and a water immiscible solvent.12. The method of wherein the base is derived from the coupling reagent and the coupling reagent is N claim 11 ,N′-carbonyldiimidazole.13. The method of step (B1) wherein the compounds of Formulae 7 and 5 are contacted in the presence of a water immiscible solvent.14. The method of wherein the acid of Formula 5 comprises hydrogen chloride.1522-. (canceled)23. The method of wherein the water immiscible solvent comprises ethyl acetate or iso-propyl acetate.24. The method of wherein the water immiscible solvent comprises ethyl acetate or iso-propyl acetate.25. The method of wherein the water immiscible solvent comprises ethyl acetate or iso-propyl acetate.26. The method of wherein the water immiscible solvent ...

METHOD FOR PREPARING 2-AMINO-N-(2,2,2-TRIFLUOROETHYL) ACETAMIDE

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. 115-. (canceled)17. The method of wherein the compounds of Formulae 1 or 1A and Formula 15 and the coupling reagent are contacted in the presence of a base and a polar aprotic water miscible solvent.18. The method of wherein the polar aprotic water miscible solvent comprises acetonitrile claim 17 , tetrahydrofuran or dioxane.19. The method of wherein the base is derived from the coupling reagent and the coupling reagent is N claim 17 ,N′-carbonyldiimidazole.20. The method of wherein the compound of Formula 15 is first contacted with the coupling reagent to form a mixture and then the compound of Formula 1 or 1A is added to the mixture in the presence of base.21. The method of wherein the compound of Formula 1 or 1A is added to the mixture as a solid or a solution in the polar aprotic water miscible solvent.22. The method of wherein the compound of Formula 1 or 1A is added to the mixture as a solution or slurry in water. This invention pertains to a method for preparing 2-amino-N-(2,2,2-trifluoroethyl)acetamide and its salts. The present invention also relates to intermediates for the aforedescribed method and use of the subject compound as a starting material in other preparative methods.The present invention provides a method for preparing a compound of Formula 1comprising (A) contacting a compound of Formula 2with a compound of Formula 3and a coupling reagent to form an intermediate of Formula 4 in the presence of a base(B) contacting the intermediate of Formula 4 with hydrogen in the presence of a hydrogenolysis catalyst to give a compound of Formula 1, and (C) optionally contacting the compound of Formula 1 with an acid of Formula ...

Process for Preparing 5-biphenyl-4-amino-2-methyl Pentanoic Acid

The present invention relates to pyrrolidin-2-ones according to the formula (1), or salts thereof, 4. A process according to claim 3 , step B claim 3 , wherein the reduction comprises treatment with hydrogen and a catalyst.5. A process according to claim 4 , wherein the catalyst is Pd/C.6. A process according to claim 5 , wherein the Pd/C catalyst is selected from the group consisting of 10% Pd/C type K-0218 claim 5 , 10% type PD CP 4505 D/R claim 5 , 5% Pd/C type 39 claim 5 , 10% Pd/C type 39 claim 5 , 10% Pd/C type 39 (7200) claim 5 , 20% Pd/C type 91 claim 5 , 10% Pd/C type 338 claim 5 , 10% Pd/C type 394 claim 5 , 10% Pd/C type 394 (6065) claim 5 , 10% Pd/C type 394 (6249) claim 5 , 10% Pd/C type 395 claim 5 , 10% Pd/C type 395 (6002) claim 5 , 10% Pd/C type mod (72595) claim 5 , 15% Pd/C type A101023 and 15% Pd/C type A502085.7. A process according to step A claim 3 , wherein the CO-activating group is selected from dimethylamino claim 3 , morpholinyl claim 3 , imidazolyl claim 3 , methylmethoxyamino claim 3 , methyl claim 3 , ethyl claim 3 , chloro claim 3 , bromo claim 3 , pivaloyl and acetyl.8. A process according to claim 7 , wherein R4 of formula (4) is morpholinyl and the biphenylic compound used in step b) is a biphenylmagnesium halide claim 7 ,orR4 of formula (4) is chloride and the biphenylic compound used in step b) is biphenyl.11. A process according to claim 3 , step D claim 3 , wherein the reaction of the compound of formula (11) with an activated biphenylic compound takes place under Fe- or Mn-catalyzed cross coupling reaction conditions.12. A process according to claim 3 , step D claim 3 , wherein the reaction of the compound of formula (11) with an activated biphenylic compound takes place in the presence of a metal salt additive.15. A process according to claim 3 , wherein any hydrogenation takes place under enantioselective hydrogenation reaction conditions. This application is a Divisional application of Ser. No. 13/333,437, filed Dec. 21, ...

PROCESS FOR PREPARATION OF PREGABALIN

Aspects of the present invention relate to improved process for preparation of (R)(−)-3-(carbamoylmethyl)-5-methylhexanoic acid (R-CMHA) of the formula (II) or its pharmaceutically acceptable salts in the presence of a lewis acid, process for preparation of pregabalin using R-CMHA of the formula (II) or its pharmaceutically acceptable salts prepared according to the present invention and process for preparation of pregabalin with low amount of undesired impurity. 2. The ammonia reagent according to step a) of is selected from NHgas claim 1 , (NH)CO claim 1 , HCONH claim 1 , Aq.NH claim 1 , NHCONH claim 1 , HCOONH claim 1 , NHCl.3. The lewis acid according to step a) of is selected from calcium chloride claim 1 , lithium chloride claim 1 , cerium chloride claim 1 , Indium chloride claim 1 , magnesium chloride claim 1 , magnesium bromide claim 1 , ammonium chloride claim 1 , zinc chloride claim 1 , boron trifluoride dietherate complex.4. The solvent according to step a) of is selected from alcohol solvents claim 1 , aliphatic or alicyclic hydrocarbon solvents claim 1 , halogenated hydrocarbon solvents claim 1 , aromatic hydrocarbon solvents claim 1 , or any mixtures thereof.6. The hypohalite according to step b) of is selected from sodium hypochlorite claim 5 , sodium hypobromite claim 5 , calcium hypochlorite claim 5 , calcium hypobromite.7. The base according to step b) of is selected from alkali metal hydroxide claim 5 , alkaline earth metal hydroxide claim 5 , alkali metal carbonate claim 5 , alkaline earth metal carbonate claim 5 , alkali metal bicarbonates.8. The solvent according to step b) of is selected from water claim 5 , alcohol claim 5 , aliphatic or alicyclic hydrocarbon claim 5 , halogenated hydrocarbon claim 5 , aromatic hydrocarbon or any mixtures thereof. This application claims priority to Indian provisional application Nos. 872/CHE/2013 filed on Feb. 28, 2013; and 4332/CHE/2013 filed on Sep. 25, 2013, all of which are hereby incorporated by ...

SYNTHESIS OF DIAMIDO GELLANTS BY USING AMINO ACID N-CARBOXYANHYDRIDES

The invention relates to a method for the synthesis of a compound according to formula I comprising the following steps: a) reacting a N-carboxyanhydride according to formula II and a N-carboxy-anhydride according to formula III with a diamine according to formula IV and b) adding an acid to the reaction to adjust the pH value of the reaction to <7; wherein L represents a C-Calkyl group, a C-Caryl group, or a C-Calkylaryl group; and Rand Rcan be identical or different and represent a hydrogen atom, a C-Calkyl group, a C-Chydroxyalkyl group, a C-Cthioether group, a C-Caryl group, a C-Calkylaryl group, a C-Calkylhydroxyaryl group, a C-Calkylheteroaryl group with 1 to 4 heteroatoms; or a C-Calkylcarboxylic moiety, which may be an acid, an amide, or which may be esterified with a C-Calkyl group or a C-Calkylaryl group. 2. Method according to claim 1 , wherein Rand Rcan be identical or different and represent a hydrogen atom claim 1 , a n-butyl group claim 1 , a t-butyl group claim 1 , a propyl group claim 1 , a cyclopropyl group claim 1 , an ethyl group claim 1 , or one of the side chains of the amino acids alanine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , methionine claim 1 , phenylalanine claim 1 , tyrosine claim 1 , tryptophan claim 1 , serine claim 1 , threonine claim 1 , glutamine claim 1 , asparagine claim 1 , esters of glutamic acid claim 1 , or esters of aspartic acid.3. Method according to claim 1 , wherein L represents a C-Clinear alkyl group claim 1 , a 1 claim 1 ,4-dimethylcyclohexyl group claim 1 , or a xylene group.4. Method according to claim 1 , wherein in step b) the pH value is adjusted to 1 to 2.5. Method according to claim 1 , wherein mixing of the reactants in step a) is carried out at a temperature of −10 to +30° C.6. Method according to claim 1 , wherein in step a) the N-carboxyanhydrides according to formulae II and III are provided in an initial total molar amount that is 2 to 3.5-fold higher than the initial molar amount ...

Process for Preparing Quinoline Derivatives

A process for preparing a compound of Formula I is disclosed, comprising the steps:

METHOD FOR PREPARING BENZOIC ACID AMIDE COMPOUND

The present invention relates to a method for preparing a benzoic acid amide compound in a high yield by presenting a novel method for preparing a benzyl amine compound to be used as a reactant and delimiting the reaction condition of each step by using the same, and the method is economically advantageous since mass production is possible. 2. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the Rand Rare a methoxy group claim 1 , and Rand Rare a hydroxyl group.3. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the base catalyst is any one selected from the group consisting of triethyl amine claim 1 , pyridine claim 1 , N claim 1 ,N-diisopropyl amine claim 1 , N-methyl morpholine and a combination thereof.4. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the benzyl amine compound of Chemical Formula 2 is used in the form of a solid hydrochloride.5. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the adamantanyl benzoic anhydride of Chemical Formula 3 is in the form of mixed anhydride.6. The method for preparing a benzoic acid amide derivative of claim 1 , wherein the amide coupling reaction is performed under at least one a solvent selected from the group consisting of dichloromethane claim 1 , chloroform claim 1 , 1 claim 1 ,2-dichloroethane claim 1 , 1 claim 1 ,1 claim 1 ,2-trichloroethane claim 1 , chlorobenzene and a combination thereof.8. The method for preparing a benzyl amine compound of claim 7 , wherein theaqueous alkaline solution in the T1) step comprises a at least one base selected from the group consisting of sodium carbonate claim 7 , sodium bicarbonate claim 7 , potassium carbonate claim 7 , potassium bicarbonate and a combination thereof.9. The method for preparing a benzyl amine compound of claim 7 , wherein the reducing agent in the T2) step is zinc.10. The method for preparing a benzyl amine compound of claim 7 , wherein the ...

Composition of 5-Nitrobenzoate Derivatives as Anti-Metastatic Agent that Inhibits Tumor Cell-Induced Platelet Aggregation

Disclosed are 5-nitrobenzoate derivatives of Formula I, 1. (canceled)2. (canceled)6. The 5-nitrobenzoate derivative according to being prepared as a pharmaceutical composition.7. The 5-nitrobenzoate derivative according to being prepared as a pharmacologically acceptable salt. The application claims the benefit of Taiwan Patent Application No. 101124690, filed on Jul. 9, 2012, in the Taiwan Intellectual Property Office, the disclosures of which are incorporated herein in their entirety by reference.The present invention relates to a 5-nitrobenzoate derivative which is used in the therapy for cancer metastasis via the inhibition of tumor cell-induced platelet aggregation (TCIPA).Tumor cells can stimulate platelet activation and form the aggregation complex with platelets in the vascular circulation system. This interaction is termed as tumor cell-induced platelet aggregation (TCIPA). The ability of tumor cells to induce platelet aggregation has been proven to highly correlate with the metastatic capability of malignant tumor. At present, it is known that there are many factors and mechanisms involved in TCIPA. For instance, tumor cells activate coagulation cascade via thrombin generation and induce platelet aggregation. Besides, adenosine diphosphate (ADP) release is involved in MCF-7 tumor cells-induced platelet aggregation that is relevant to the expression of platelet surface P2Y12 receptor (Alonso-Escolano et al., Br. J. Pharmacol. 141: 241-252, 2004). Other factors including (1) proteinases: cathepsin B and matrix metalloprotease (MMPs), (2) thromboxane A2 and prostacyclin, (3) nitric oxide (NO), (4) platelet surface proteins (e.g. GPIb-IX-V, GPIIb/IIIa and P-selectin, etc.) and so on are involved in TCIPA (Jurasz et al., Br. J. Pharmacol. 143: 819-826, 2004). Based on these results, the detail mechanism of TCIPA seems to very complicated and still be obscured. Nevertheless, these results highlight TCIPA as a target for development of cancer therapeutic ...

METHODS OF MANUFACTURING BENZOQUINOLINE COMPOUNDS

The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof. 2. The process of wherein Yis C-Calkoxy.3. The process of wherein Yis ethoxy.4. The process of wherein Yis acetoxy.5. The process of wherein Yis selected from the group consisting of fluorine claim 1 , chlorine claim 1 , and bromine.6. The process of wherein said base is selected from the group consisting of alkali metal alkoxides claim 1 , alkali metal hydroxides claim 1 , alkali metal hydrides claim 1 , alkali metal carbonates claim 1 , and trialkylamines.7. The process of wherein said base is an alkali metal alkoxide.8. The process of wherein said base is sodium tert-butoxide.10. The process of wherein Yis iodide or methylsulfate.11. The process of wherein Yis iodide.12. The process of wherein said base is selected from the group consisting of alkali metal carbonates claim 9 , alkali metal bicarbonates claim 9 , alkali metal alkoxides claim 9 , alkali metal hydroxides claim 9 , alkali metal hydrides claim 9 , and trialkylamines.13. The process of wherein said base is an alkali metal carbonate.14. The process of wherein said base is potassium carbonate.15. The process of wherein said solvent is selected from the group consisting of acetone claim 9 , acetonitrile claim 9 , dimethyl formamide claim 9 , 2-methyltetrahydrofuran claim 9 , and tetrahydrofuran.16. The process of wherein said solvent is acetone.17. The process of wherein the volume of said solvent is between about 5 to about 15 times the mass of the compound of Formula IV.18. The process of wherein the volume of said solvent is about 8 times the mass of the compound of Formula IV.19. The process of wherein said reaction step is carried out in the presence of a phase transfer catalyst that is selected from the group consisting of tetrabutylammonium bromide claim 9 , tetrabutylammonium iodide claim 9 , and 18-crown-6.20. The process of wherein said ...

PREPARATION METHOD AND USE OF N-ACYL ACIDIC AMINO ACID OR SALT THEREOF

The invention provides a preparation method of N-acyl acidic amino acid or a salt thereof, comprising subjecting a fatty acyl chloride and an amino acid to an amidation reaction under an alkaline condition. The preparation method is characterized in that in the amidation reaction, water is used as a solvent, an acidic amino acid or a salt thereof is used as a main raw material and a small amount of a neutral amino acid or a salt thereof is used as an auxiliary raw material, and the method comprises the following steps: under a stirring condition, firstly adding the fatty acyl chloride dropwise into an aqueous solution of the acidic amino acid or the salt thereof; adding an alkali to adjust the pH value of the reaction solution; after a certain amount of fatty acyl chloride having been added dropwise, adding an aqueous solution of the neutral amino acid or the salt thereof, and continuing to add the fatty acyl chloride dropwise until the addition is finished and stirring to maintain the reaction. The preparation method uses the reaction of the mixed amino acids and the fatty acyl chloride under a water-phase system, so that the conversion rates of the amino acids and the acyl chloride can be remarkably increased and the amount of residual amino acids is greatly reduced. The product can be directly used as a surfactant after simple post-treatment, and thus the cost is greatly reduced. 110-. (canceled)11. A method of preparing an N-acyl acidic amino acid or a salt thereof , comprising:subjecting a fatty acid chloride and an amino acid to an amidation reaction under a basic condition, characterized in that, the amidation reaction uses water as a solvent, an acidic amino acid or a salt thereof as a main reactant and a small amount of a neutral amino acid or a salt thereof as an auxiliary reactant; while stirring, first adding the fatty acid chloride gradually into an aqueous solution of the acidic amino acid or a thereof; adding a base to adjust the pH value of the ...

PROCESS FOR PREPARING N-ALKYL(METH)ACRYLAMIDES

The invention relates to a process for preparing N-alkyl(meth)acrylamides by reacting (meth)acrylic anhydride with corresponding alkylamines. 2. (canceled)3. The process according to claim 1 , wherein the alkylamine is precooled to below 30° C. claim 1 , before said reacting.4. The process according to claim 1 , further comprising:diluting the reaction solution comprising the N-alkyl(meth)acrylamide and (meth)acrylic acid with water, optionally with a centrifuge mother liquor,subsequently neutralizing the reaction solution using an alkaline solution, thereby obtaining a precipitated N-alkyl(meth)acrylamide, andseparating the precipitated N-alkyl(meth)acrylamide.5. The process according to claim 4 , wherein said reacting and said neutralizing are each carried out in a separate vessel.6. (canceled)7. The process according to claim 1 , wherein a concentration of the alkylamine in the aqueous solution is 50-90%.8. The process according to claim 1 , wherein said reacting is carried out in the presence of water-soluble polymerization inhibitors which act under inert gas.9. The process according to claim 1 , further comprising:milling a product crystal slurry obtained after said reacting in a mill before said separating in a centrifuge.10. The process according to claim 1 , wherein the reaction vessel is equipped with an external heat exchanger and a circulation pump.11. (canceled) The invention relates to a process for preparing N-alkyl(meth)acrylamides by reacting (meth)acrylic anhydride with corresponding alkylamines.The preparation of N-alkyl(meth)acrylamides is known. The Ritter reaction has for a long time been employed for preparing amides from nitriles and substrates which can form carbenium ions, e.g. tertiary or secondary alcohols, in the presence of strong mineral acids. DE 3131096 utilizes this process. A disadvantage is that the acid, which also functions as solvent, has to be neutralized and large amounts of salts are thus obtained. Furthermore, the product ...

TRPV1 Modulator Compounds

The present invention relates to TRPV1 modulator compounds of formula (I) or their pharmaceutically, veterinary or cosmetically acceptable salts, or their stereoisomers or mixtures thereof, wherein m is an integer selected from 1 to 3; R, R, Rand R are independently selected from H, (C-C)alkyl, unsaturated (C-C)hydrocarbon, and (C-C)cycloalkyl, being these groups optionally substituted; Ris hydrogen or halogen; Ris selected from H, (C-C)alkyl, unsaturated (C-C)hydrocarbon, (C-C)cycloalkyl, (C-C)aryl, and (C-C)heteroaryl, being these groups optionally substituted; and Ris selected from (C-C)alkyl, unsaturated (C-C)hydrocarbon, (C-C)aryl, and (C-C)heteroaryl, being these groups optionally substituted. It also relates to a process for their preparation, to pharmaceutical, veterinary or cosmetic compositions containing them, and to their pharmaceutical, veterinary and cosmetic applications. 115-. (canceled)17. The compound of formula (I) according to claim 16 , wherein m is an integer selected from 1 to 2.18. The compound of formula (I) according to claim 16 , wherein Ris selected from the group consisting of H claim 16 , optionally substituted (C-C)alkyl claim 16 , and optionally substituted unsaturated (C-C)hydrocarbon.19. The compound of formula (I) according to claim 18 , wherein Ris selected from the group consisting of H claim 18 , optionally substituted (C-C)alkyl claim 18 , and optionally substituted unsaturated (C-C)hydrocarbon.20. The compound of formula (I) according to claim 18 , wherein Ris selected from the group consisting of optionally substituted (C-C)alkyl claim 18 , and optionally substituted unsaturated (C-C)hydrocarbon.21. The compound of formula (I) according to claim 18 , wherein Rand R are independently selected from the group consisting of H claim 18 , optionally substituted (C-C)alkyl claim 18 , and optionally substituted unsaturated (C-C)hydrocarbon.22. The compound of formula (I) according to claim 16 , wherein Ris H.23. The compound of ...

METHOD OF PRODUCING N,N-DISUBSTITUTED AMIDE AND CATALYST FOR PRODUCING N,N-DISUBSTITUTED AMIDE

A method of producing an N,N-disubstituted amide of the present invention is a method of reacting a nitrile with an alcohol in the presence of a catalyst, wherein the nitrile is a compound represented by RCN (Rrepresents an alkyl group having 10 or less carbon atoms or an aryl group having 10 or less carbon atoms), wherein the alcohol is a compound represented by ROH (Rrepresents an alkyl group having 10 or less carbon atoms), wherein the catalyst is a metal salt represented by MXn (M represents a metal cation having an oxidation number of n, X represents a monovalent anion including a substituted sulfonyl group represented by —S(═O)—R(Rrepresents a hydrocarbon group having 10 or less carbon atoms or a group in which some or all of hydrogen atoms in the hydrocarbon group are substituted with fluorine atoms), and n represents an integer of 1 to 4), a substituent bonded to a carbon atom in a carbonyl group of the N,N-disubstituted amide is R, and two substituents bonded to nitrogen atoms in an amide group are both R. 1. A method of producing an N ,N-disubstituted amide by reacting a nitrile with an alcohol in the presence of a catalyst , {'br': None, 'sup': '1', 'RCN'}, 'wherein the nitrile is a compound represented by'}{'sup': '1', '(in the formula, Rrepresents an alkyl group having 10 or less carbon atoms or an aryl group having 10 or less carbon atoms),'} {'br': None, 'sup': '2', 'ROH'}, 'wherein the alcohol is a compound represented by'}{'sup': '2', '(in the formula, Rrepresents an alkyl group having 10 or less carbon atoms),'} {'br': None, 'MXn'}, 'wherein the catalyst includes a metal salt represented by'}{'sub': '2', 'sup': 3', '3, '(in the formula, M represents a metal cation having an oxidation number of n, X represents a monovalent anion including at least one substituted sulfonyl group represented by —S(═O)—R(in the formula, Rrepresents a hydrocarbon group having 10 or less carbon atoms or a group in which some or all of hydrogen atoms in the hydrocarbon ...

METHOD FOR PRODUCING ALPHA,BETA-UNSATURATED CARBOXYLIC ACID-N,N-DISUBSTITUTED AMIDE AND METHOD FOR PRODUCING 3-ALKOXYCARBOXYLIC ACID-N,N-DISUBSTITUTED AMIDE

The invention is directed to a technique for effectively producing an amide compound suitable for use as a solvent or a detergent on a large scale and at low cost. 1. A method for producing an α ,β-unsaturated carboxylic acid-N ,N-disubstituted amide , the method comprising:adding a vapor-phase-polymerization inhibitor to an N,N-disubstituted-β-amino acid-N′,N′-disubstituted amide in liquid form;decomposing the N,N-disubstituted-β-amino acid-N′,N′-disubstituted amide at 200 to 300° C. and at a pressure of 0.15 to 0.95 MPa, to thereby produce an α,β-unsaturated carboxylic acid-N,N-disubstituted amide in vapor form; andadding a liquid-phase-polymerization inhibitor to the α,β-unsaturated carboxylic acid-N,N-disubstituted amide.2. The method of claim 1 , wherein the vapor-phase-polymerization inhibitor comprises at least one polymerization inhibitor selected from the group consisting of N-nitrosophenylhydroxylamine ammonium salt claim 1 , N-nitrosophenylhydroxylamine aluminum salt claim 1 , N-nitrosophenylhydroxylamine zinc salt claim 1 , and N-nitrosophenylhydroxylamine iron salt claim 1 , andwherein the liquid-phase-polymerization inhibitor comprises at least one polymerization inhibitor selected from the group consisting of copper dithiocarbamate, phenothiazine, hydroquinone, benzoquinone, and hydroquinone monomethyl ether.3. The method of claim 1 , wherein the vapor-phase-polymerization inhibitor is added in an amount of 0.06 to 2 mass % with respect to the N claim 1 ,N-disubstituted-β-amino acid-N′ claim 1 ,N′-disubstituted amide.4. The method of claim 1 , wherein the liquid-phase-polymerization inhibitor is added in an amount of 100 to 10 claim 1 ,000 mass ppm with respect to the α claim 1 ,β-unsaturated carboxylic acid-N claim 1 ,N-disubstituted amide.5. The method of claim 1 , wherein the N claim 1 ,N-disubstituted-β-amino acid-N′ claim 1 ,N′-disubstituted amide is decomposed in the presence of at least one solid acid catalyst selected from the group consisting ...

INSTALLATION AND PROCESS FOR THE PREPARATION OF HYDROGEN CYANIDE

Present invention relates to a process and an installation () for the preparation of hydrogen cyanide by the Andrussow process, and more precisely for improving the conditions of mixing the reactant gases before feeding the Andrussow type reactor (), in order to improve safety, to avoid any risk of explosion and to produce HCN in safe and efficient manner. The installation is configured in such a manner that oxygen is pre-mixed with air with a ratio comprised between 20.95% and 32.5% by volume, preferably between 25% and 30.5% by volume; methane containing gas and ammonia are simultaneously added in the pre-mixture of oxygen-enriched air in such a manner that the volumic ratio of methane to ammonia is comprised between 1.35 and 1.02 depending on the content of oxygen into air; said obtained reactant gases mixture having a temperature comprised between 80° C. and 120° C., preferably between 95° C. and 115° C. for feeding the Andrussow type reactor (). 1100. An installation () for the preparation of hydrogen cyanide HCN , said installation comprising:{'b': 60', '60, 'A) an Andrussow type reactor (), in which is introduced a reactant gases mixture of methane-containing gas, ammonia and oxygen-enriched air, said mixture reacting inside said reactor () over a catalyst to produce HCN,'}{'b': 60', '1', '4', '1', '1, 'B) upstream of said Andrussow type reactor () according to the direction of gas flow, gas feeding pipes (P to P) for feeding the installation with each reactant gas, a first unit (U) for pre-mixing oxygen with air before adding methane-containing gas and ammonia into the obtained pre-mixture of oxygen-enriched air, wherein said first unit (U) comprises at least one oxygen online controller so as to control the ratio of oxygen into air, said ratio of oxygen to air comprising between 20.95% and 32.5% in volume of oxygen;'}{'b': '2', 'C) a second unit (U) for adding simultaneously methane-containing gas and ammonia into the oxygen-enriched air, with a volumic ...

Catalyst, Method for Forming Amide Bond, and Method for Producing Amide Compound

A catalyst represented by General Formula (1) below: 2. The catalyst according to claim 1 , wherein the substituent is an electron donative group or an electron attractive group.4. A method for forming an amide bond claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'reacting a carboxyl group of a carboxylic acid compound with an amino group of an amine compound in the presence of the catalyst according to to form the amide bond.'}5. A method for producing an amide compound claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'reacting a carboxylic acid compound with an amine compound in the presence of the catalyst according to to obtain the amide compound.'} The present invention relates to a novel catalyst, a method for forming an amide bond using the catalyst, and a method for producing an amide compound using the same.An amide bond is a basic constitutional unit of synthesized polymers such as biopolymers (e.g., proteins) and nylons and is contained in 25% of synthesized pharmaceuticals. Therefore, the amide bond forming reaction has considerably high industrial usability (see NPL 1).The amide bond forming reaction is generally performed using a stoichiometric activator. Use of such an activator generates a desired amide, while there is a problem that a large amount of waste products are formed as a by-product.Then, the working group, which consists of a plurality of pharmaceutical companies that belong to American Chemical Society Green Chemistry Institute, selects “the amide bond forming reaction that generates less waste products” as reaction that should be the most desirably developed in 2006 (see NPL 2).In recent years, catalytic amide bond forming reaction has been considered and has been proposed (see NPL 3).For example, reaction using an enzymatic catalyst has been proposed. In this reaction, however, there is a problem that an applicable range of a substrate with respect to the enzyme is ...

Process for Preparing Quinoline Derivatives

A process for preparing a compound of Formula I is disclosed, comprising the steps: 2. The process for claim 1 , wherein the polar aprotic solvent is selected form the group consisting of dichloromethane claim 1 , tetrahydrofuran claim 1 , ethyl acetate claim 1 , isopropyl acetate claim 1 , acetone claim 1 , dimethylformamide claim 1 , acetonitrile claim 1 , and dimethylsulfoxide claim 1 , or combinations thereof.3. The process for claim 1 , wherein the polar aprotic solvent is isopropyl acetate.4. The process for claim 1 , wherein approximately 5 to 10 volumes of polar aprotic acid are used relative to volume of 1 claim 1 ,1-cyclopropanedicarboxylic acid that is used.5. The process for claim 1 , wherein approximately 8 volumes of polar aprotic acid are used relative to volume of 1 claim 1 ,1-cyclopropanedicarboxylic acid that is used.6. The process for claim 1 , wherein approximately 1.01 to 1.2 molar equivalents of thionyl chloride are used.7. The process for claim 1 , wherein approximately 1.05 molar equivalents of thionyl chloride are used.8. The process for claim 1 , wherein the mixture of step (a) is stirred at ambient temperature for 2 to 24 hours.9. The process for claim 1 , wherein the mixture of step (a) is stirred at approximately 24-26° C. for 6 to 16 hours.10. The process for claim 1 , wherein the optionally substituted aniline and the tertiary amine base is added as a mixture in a polar aprotic solvent to the step (a) mixture.11. The process for claim 10 , wherein the aniline is 4-fluoroaniline and the tertiary amine base is triethyl amine.12. The process for claim 10 , wherein approximately 1.01 to 1.5 molar equivalents of aniline are used relative to the number of moles of 1 claim 10 ,1-cyclopropanedicarbopxylic acid that are used and approximately 1.01 to 1.5 molar equivalents of tertiary amine base are used relative to the number of moles of 1 claim 10 ,1-cyclopropanedicarbopxylic acid that are used.13. The process for claim 10 , wherein the polar ...

METHODS OF MANUFACTURING BENZOQUINOLINE COMPOUNDS

The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof. 2. The process of wherein Yis C-Calkoxy.3. The process of wherein Yis ethoxy.4. The process of wherein Yis acetoxy.5. The process of wherein Yis selected from the group consisting of fluorine claim 1 , chlorine claim 1 , and bromine.6. The process of wherein said base is selected from the group consisting of alkali metal alkoxides claim 1 , alkali metal hydroxides claim 1 , alkali metal hydrides claim 1 , alkali metal carbonates claim 1 , and trialkylamines.7. The process of wherein said base is an alkali metal alkoxide.8. The process of wherein said base is sodium tert-butoxide.10. The process of wherein Yis iodide or methylsulfate.11. The process of wherein Yis iodide.12. The process of wherein said base is selected from the group consisting of alkali metal carbonates claim 9 , alkali metal bicarbonates claim 9 , alkali metal alkoxides claim 9 , alkali metal hydroxides claim 9 , alkali metal hydrides claim 9 , and trialkylamines.13. The process of wherein said base is an alkali metal carbonate.14. The process of wherein said base is potassium carbonate.15. The process of wherein said solvent is selected from the group consisting of acetone claim 9 , acetonitrile claim 9 , dimethyl formamide claim 9 , 2-methyltetrahydrofuran claim 9 , and tetrahydrofuran.16. The process of wherein said solvent is acetone.17. The process of wherein the volume of said solvent is between about 5 to about 15 times the mass of the compound of Formula IV.18. The process of wherein the volume of said solvent is about 8 times the mass of the compound of Formula IV.19. The process of wherein said reaction step is carried out in the presence of a phase transfer catalyst that is selected from the group consisting of tetrabutylammonium bromide claim 9 , tetrabutylammonium iodide claim 9 , and 18-crown-6.20. The process of wherein said ...

Asymmetric Bisamidation of Malonic Ester Derivatives

The present invention relates to processes, process steps and intermediates useful in the asymmetric bisamidation of malonic ester derivatives wherein the new processes, process steps and intermediates are, for example, useful in the preparation of asymmetric malonic acid bisanilides such as cabozantinib. 4. The process of claim 1 , wherein Mis Mg claim 1 , Na or K.8. The process of claim 7 , wherein the amide bond is formed by{'sub': b', '2', '2, '(ii.a.2) reacting the compound of formula (III) and/or of formula (III′) with an Msalt of the compound HN—X;'}{'sub': 'b', 'wherein Mis an alkali or alkaline earth metal.'}9. The process of claim 1 , wherein the amide bond is formed by{'sub': b', '2', '2, '(ii.b.1) reacting the compound of formula (II) and/or of formula (II′) with an Msalt of a compound HN—X;'}{'sub': 'b', 'wherein Mis an alkali or alkaline earth metal.'}11. (canceled)12. The process of claim 10 , wherein Rand R claim 10 , together with the C atom at which Rand Rare attached claim 10 , form a cycle having 3 carbon atoms. The present invention relates to processes, process steps and intermediates useful in the asymmetric bisamidation of malonic ester derivatives. The new processes, process steps and intermediates are, for example, useful in the preparation of asymmetric malonic acid bisanilides, such as cabozantinib.Asymmetric bisanilides of disubstituted malonic acids are a structural motif present in a novel class of tyrosine kinase inhibitors in clinical investigation such as altiratinib, cabozantinib, foretinib, golvatinib, and sitravatinib (MG-516). One of these compounds, N-{4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl}-N′-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide (international non-proprietary name (INN): cabozantinib) represented by chemical structureis a RET, MET, KIT and VEGFRreceptor tyrosine kinase inhibitor. It is currently marked for the treatment of thyroid cancer under the brand name Cometriq. Cabozantinib is classified as a BCS class II ...

Novel synthesis method for the preparation of dibenzoate compounds, such as 4-[benzoyl(methyl)amino]pentane-2-yl dibenzoate

The present invention relates to a process for synthesis of a compound according to Formula (A): wherein R 1 is a substituted or unsubstituted aryl having 6 to 20 carbon atoms; preferably substituted or unsubstituted phenyl; R 2 is a straight or branched alkyl having 1 to 12 carbon atoms; and R 3 is a straight or branched alkyl having 1 to 12 carbon atoms; starting from a di-keto compound according to Formula (B) wherein R 3 is as shown above, which compound is converted into a ketoenamine compound according to Formula (C) wherein R 2 and R 3 are as shown above, which ketoenamine compound is then reduced to an amino alcohol according to Formula (D), wherein R 2 and R 3 are as shown above, that is subsequently converted into a compound according to Formula (A): characterized in that the ketoenamine is reduced into an amino alcohol using a nickel aluminium alloy in an aqueous solution of an inorganic base.

PSEUDO-CERAMIDE COMPOUND AND PREPARATION METHOD THEREFOR

The present invention relates to a pseudo-ceramide compound and a preparation method therefor. According to the present invention, the pseudo-ceramide compound has a molecular structure and a function similar to those of a natural ceramide, can be readily synthesized, and has excellent solubility in an organic solvent and excellent stability, and thus the pseudo-ceramide compound can be used as an alternative to a natural ceramide. Therefore, the pseudo-ceramide compound of the present invention can be widely applied to a skin preparation for external use, a cosmetic composition, and the like for reinforcing and maintaining a skin barrier function. 2. The pseudo-ceramide compound according to claim 1 , wherein Rand Rare the same as or different from each other and are each independently a C13 to C18 saturated or unsaturated aliphatic chain.3. The pseudo-ceramide compound according to claim 1 , wherein the pseudo-ceramide compound is hexadecanoic acid (2-hexadecyloxy-1 claim 1 ,1-bis-hydroxymethyl-ethyl)-amide claim 1 , hexadecanoic acid (1 claim 1 ,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide claim 1 , hexadecanoic acid (1 claim 1 ,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide claim 1 , octadecanoic acid (2-hexadecyloxy-1 claim 1 ,1-bis-hydroxymethyl-ethyl)-amide claim 1 , octadecanoic acid (1 claim 1 ,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide claim 1 , octadecanoic acid (1 claim 1 ,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide claim 1 , tetradecanoic acid (2-hexadecyloxy-1 claim 1 ,1-bis-hydroxymethyl-ethyl)-amide claim 1 , or tetradecanoic acid (1 claim 1 ,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide.5. The method for preparing the pseudo-ceramide compound according to claim 4 , wherein the Rand Rare the same as or different from each other and are each independently a C13 to C18 saturated or unsaturated aliphatic chain.6. The method for preparing the pseudo-ceramide compound according to claim 4 , wherein the compound of Chemical Formula 4 is ...

Method for Making Two-Phase Solution of which Phase State Changes as a Result of Temperature Conversion React, and Apparatus for Implementing This

A method for making a number (N) of samples react under the same reaction conditions, wherein the samples have a solution where the phase state of a reaction solvent changes in a reversible manner between a two-phase solution state and a uniform solution state when the temperature fluctuates over or under a certain constant temperature, and the processes are carried out sequentially in the following steps: (A) the constant container heating step of heating a number of reaction containers simultaneously and maintaining the reaction containers at a predetermined temperature; (B) the sample heating step of putting a sample in each heated reaction container and of maintaining a two-phase solution at a predetermined temperature; (C) the reaction step of stirring the sample that has been heated to the predetermined temperature so as to gain a uniform solution, which is maintained for a predetermined period of time; (D) the cooling step of cooling the uniform solution without cooling the reaction container after the predetermined period of time has passed so as to gain a two-phase solution within the reaction container. 1. (canceled)2. A method , comprising:heating a material solution comprising a reactant and a two-phase reaction solvent comprising a first phase comprising a nonpolar solvent and a second phase comprising a polar solvent to a reaction temperature in a reaction container;stirring the material solution, such that the first phase and the second phase of the two-phase reaction solvent dissolve each other to form a one-phase solution;maintaining the one-phase solution, with stirring, at the reaction temperature for a predetermined period of time, to obtain a one-phase product solution comprising a reaction product; andcooling the one-phase product solution within the reaction container inside the reaction container to a predetermined temperature below the reaction temperature without cooling the reaction container, to obtain a two-phase product solution ...

Synthesis and anti-tumor activities of acyl-para-aminophenol derivatives

Method are disclosed for synthesizing derivatives of acyl-para-aminophenol and for the use of the compounds for treating lymphomas and tumors of the brain and spinal cord.

METHOD FOR PRODUCING (METH)ACRYLIC ACID AMIDE COMPOUND, COMPOSITION, AND ACTIVE ENERGY RAY-CURABLE COMPOSITION

A method for producing a (meth)acrylic acid amide compound, the method including: adding at least one selected from the group consisting of an amino group-containing compound and a neutralization salt of the amino group-containing compound to a mixture including (meth)acrylic acid halide and an organic solvent immiscible with water to allow the (meth)acrylic acid halide and at least one selected from the group consisting of the amino group-containing compound and the neutralization salt of the amino group-containing compound to react with each other, to produce the (meth)acrylic acid amide compound. 1. A method for producing a (meth)acrylic acid amide compound , the method comprisingadding at least one selected from the group consisting of an amino group-containing compound and a neutralization salt of the amino group-containing compound to a mixture including (meth)acrylic acid halide and an organic solvent immiscible with water to allow the (meth)acrylic acid halide and at least one selected from the group consisting of the amino group-containing compound and the neutralization salt of the amino group-containing compound to react with each other, to produce the (meth)acrylic acid amide compound.2. The method according to claim 1 , wherein at least one selected from the group consisting of the amino group-containing compound and the neutralization salt of the amino group-containing compound is an aqueous solution of at least one selected from the group consisting of the amino group-containing compound and the neutralization salt of the amino group-containing compound.3. The method according to claim 1 , further comprising adding an alkaline aqueous solution after adding at least one selected from the group consisting of the amino group-containing compound and the neutralization salt of the amino group-containing compound to the mixture.4. The method according to claim 1 , wherein solubility of the organic solvent in water is 30 g/100 mL or less.5. The method ...

PROCESS FOR THE PREPARATION OF (1S,2R)-MILNACIPRAN

The invention relates to a process for the preparation of Levomilnacipran or salts thereof, compounds useful in the treatment of depression, with high yield. 2. The process according to claim 1 , comprising an additional step b′) carried out after step b) claim 1 , consisting of treating said Levomilnacipran with an inorganic base.3. The process according to claim 1 , wherein in step a) the amount of phthalimide comprises between 1 and 1.05 equivalents with respect to the molar amount of alcohol (D) used.4. The process according to claim 1 , wherein step a) is carried out in an aprotic polar solvent selected from the group consisting of a chlorinated solvents and an ethers.5. The process according to claim 1 , wherein step b) is carried out by treatment with a compound selected from the group consisting of hydrazine claim 1 , an alkylamine and a hydroxyalkylamine.6. The process according to claim 5 , wherein the amount of hydrazine claim 5 , alkylamine or hydroxyalkylamine comprises between 2 and 25 equivalents with respect to the molar amount of the phthalimido derivative (C).7. The process according to claim 2 , wherein the inorganic base used in step b′) is selected from the group consisting of a carbonates and a hydroxides.10. The process according to claim 9 , wherein steps a′)-c) of the process are carried out without isolation of the intermediate compounds. The present invention relates to an industrially applicable and advantageous process for the preparation of (1S,2R)-Milnacipran (generally known as Levomilnacipran) or a salt thereof.(1S,2R)-2-aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide, also known as Levomilnacipran, is an active principle useful in the treatment of depression for its ability to act as an inhibitor of the reuptake of serotonin-norepinefphrine. Said compound is characterized by the following structural formula:The preparation of Milnacipran (i.e. the racemic form of Levomilnacipran) or salts thereof has been widely described ...

ALTERNATIVE PROCESS FOR THE PURIFICATION OF AN INTERMEDIATE IN THE SYNTHESIS OF NON-IONIC X-RAY CONTRAST AGENTS

Alternative continuous downstream processes for the production of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”) are described. Compound A is a key intermediate in the production of iodixanol and iohexol, which are two of the biggest commercially available non-ionic x-ray contrast media agents. 1. A process comprising the steps of:(i) reacting 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound B”) with a mixture of acetic anhydride/acetic acid to form a slurry;(ii) heating said slurry to about 60° C.;(iii) adding an acid catalyst to said slurry at a rate such that the reaction temperature is maintained at a temperature range of about 65-85° C.;(iv) adding a deactylating agent to the reaction mixture of step (iii) to form a reaction mixture comprising Compound A;(v) purifying the reaction mixture of step (iv) comprising Compound A wherein said purifying step comprises the steps of:(vi) passing said reaction mixture of step (iv) comprising Compound A through a membrane filtration system;(vii) collecting the retentate of step (vi) and repeating step (v); and(viii) continuously repeating steps (v)-(vii).2. The process according to claim 1 , wherein said membrane filtration system comprises a nanofiltration system.3. The process according to or claim 1 , wherein step (viii) is repeated until until the level of salts is not more than (NMT) 1.5 wt % and the level of by-products is NMT 2.0 area % in the Compound A solution into the alkylation step.4. The process according to claim 1 , further comprising the step of:alkylating the reaction mixture of step (iv) comprising Compound A.5. The process according to claim 1 , further comprising the step of:bis-alkylating or dimerizing the reaction mixture of step (iv) comprising Compound A.6. The process according to wherein said acid catalyst is a sulfonic acid.7. The process according to claim 6 , wherein said acid catalyst is para-toluene sulfonic acid (PTSA).8. The ...

PROCESS FOR THE PREPARATION OF PROTECTED L-ALANINE DERIVATIVES

The present invention is directed to a novel process for the preparation of protected L-alanine derivatives, useful as intermediates in the synthesis of compounds useful as mu/delta opioid modulators. 2. The process as in claim 1 , wherein the oxidizing agent is selected from the group consisting of hydrogen peroxide claim 1 , LiOH and LiOOH.3. The process as in claim 2 , wherein the oxidizing agent is hydrogen peroxide.4. The process as in claim 1 , wherein the oxidizing agent is 30% hydrogen peroxide and is present in an excess amount.5. The process as in claim 1 , wherein the inorganic base is potassium carbonate.6. The process as in claim 1 , wherein the inorganic base is present in an amount in the range of from about 1.0 to about 3.0 molar equivalents.7. The process as in claim 1 , wherein the third organic solvent is DMSO.8. The process as in claim 1 , wherein the compound of formula (I-B) is reacted with the oxidizing agent at a temperature in the range of from about room temperature to about 60° C.9. A compound prepared according to a process as in . This application is a continuation of U.S. Ser. No. 14/162,150, filed Jan. 23, 2014 (now allowed), which is a divisional of U.S. Ser. No. 12/606,730, filed Oct. 27, 2009 (now U.S. Pat. No. 8,710,256, issued Apr. 29, 2014), which is derived from and claims priority to U.S. Provisional App. No. 61/108,649, filed Oct. 27, 2008, the entire contents of each of which are incorporated herein by reference.The present invention is directed to a novel process for the preparation of protected L-alanine derivatives, useful as intermediates in the synthesis of compounds useful as mu/delta opioid modulators.The opioid receptors were identified in the mid-1970's, and were quickly categorized into three sub-sets of receptors (mu, delta and kappa). More recently the original three types of receptors have been further divided into sub-types. Also known is that the family of opioid receptors are members of the G-protein coupled ...

Alternative process for the purification of an intermediate in the synthesis of non-ionic x-ray contrast agents

Alternative continuous downstream processes for the production of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”) are described. Compound A is a key intermediate in the production of iodixanol and iohexol, which are two of the biggest commercially available non-ionic x-ray contrast media agents.

ALTERNATIVE ACETYLATION PROCESS IN THE SYNTHESIS OF NON-IONIC X-RAY CONTRAST AGENTS

An alternative acetylation process for the synthesis of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”), an intermediate in the industrial preparation of non-ionic X-ray contrast agents, is described. The process can be performed on an industrial scale to produce Compound A with improved purity and improved yields compared to the established processes. 1. A process comprising the steps of:(i) reacting 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound B”) with a mixture of acetic anhydride/acetic acid to form a slurry;(ii) heating said slurry to about 60° C.; and(iii) adding an acid catalyst to said slurry at a rate such that the reaction temperature is maintained at a temperature range of about 65-85° C.2. The process according to claim 1 , further comprising the step of:(iv) adding a deacetylating agent to the reaction mixture of step (iii).3. The process according to claim 2 , further comprising the step of:(v) purifying the reaction mixture of step (iv).4. The process according to claim 3 , wherein said purifying step is a crystallization step.5. The process according to claim 4 , wherein said crystallization step achieved by seeding with Compound A.6. The process according to wherein said acid catalyst is a sulfonic acid.7. The process according to claim 6 , wherein said acid catalyst is para-toluene sulfonic acid (PTSA).8. The process according to claim 7 , wherein said PTSA is added in a catalytic amount as a solid.9. The process according to claim 7 , wherein said PTSA is added in a catalytic amount as a solution of PTSA dissolved in a small volume of acetic anhydride. This invention relates generally to large-scale synthesis of non-ionic X-ray contrast agents. It further relates to an alternative acetylation process for the synthesis of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”), an intermediate in the industrial preparation of non-ionic X-ray contrast ...

Continuous Process For Producing A Surfactant In A Tube Reactor

The invention relates to a continuous method for producing a tenside, containing a compound of the formula (1), wherein Ris a fatty acid alkyl residue and Ris a linear or branched Cto Chydrocarbon residue, and x is in the range from 1 to 15 by conversion of fatty acid alkyl esters or fatty acid triglycerides having an N-n-alkylized polyhydroxy compound in the presence of an alkali catalyst or a catalyst selected from hydroxides or alcoholates of the 2nd and 4th secondary group of the periodic system at a temperature in the range from 40 to 300° C. 2. The continuous process as claimed in claim 1 , wherein the continuous process comprises the following steps:1. mixing an aqueous raw material solution comprising at least one N-n-alkylated polyhydroxy compound with the catalyst to form an aqueous solution;2. drying the aqueous solution, wherein the water content after drying being in the range of 0-5 wt % to form a dried mixture;3. heating the dried mixture to a temperature in the range from 60 to 180° C. to form a melt, and mixing the melt with fatty acid alkyl esters or triglycerides to form a reaction mixture;4. optionally, intermediately storing and mixing the reaction mixture in a continuously operated stirred tank;5. carrying out reaction in a tube reactor; and optionally6. removing any coproducts.3. The continuous process as claimed in claim 1 , wherein the fatty acid alkyl esters or fatty acid triglycerides have a chain length of Cto C.4. The continuous process as claimed in claim 1 , wherein at least one N-n-alkylated polyhydroxy compound is a Cto CN-alkylglucamine.5. The continuous process as claimed in claim 2 , wherein the concentration of the at least one N-n-alkylated polyhydroxy compound in the aqueous solution in the first process step is in the range from 30-90% by weight.6. The continuous process as claimed in claim 1 , wherein the catalyst is used in a concentration of 0.01-5 wt %.7. The continuous process as claimed in claim 1 , wherein the molar ...

Bendamustine Derivatives and Related Compounds, and Medical Use Thereof in Cancer Therapy

The present invention relates to bendamustine derivatives and related compounds of formula (VII), (VIII) and (IX), and medical uses thereof in particular in cancer therapy. 115.-. (canceled)17. The compound of formula IX according to claim 16 , wherein the compound is in the form of a salt claim 16 , and particularly in the form of a hydrate.18. The compound of formula IX according to claim 17 , wherein the salt comprises 0.6 to 1.4 mol water relative to 1 mol of the compound claim 17 , and particularly 0.8 to 1.2 mol water relative to 1 mol of the compound.19. The compound of formula IX according to claim 16 , wherein the compound is in the form of a base addition salt in which the base is selected from the group consisting of magnesium hydroxide claim 16 , calcium hydroxide claim 16 , zinc hydroxide claim 16 , potassium hydroxide claim 16 , sodium hydroxide claim 16 , potassium carbonate claim 16 , sodium carbonate claim 16 , potassium hydrogen carbonate claim 16 , sodium hydrogen carbonate claim 16 , diethylamine claim 16 , triethylamine claim 16 , ethanolamine (2-aminoethanol) claim 16 , diethanolamine (2 claim 16 ,2′-iminobis(ethanol)) claim 16 , triethanolamine (2 claim 16 ,2′ claim 16 ,2″-nitrilotris(ethanol)) claim 16 , ethylenediamine claim 16 , piperazine claim 16 , piperidine claim 16 , pyrrolidine claim 16 , pyridine claim 16 , morpholine claim 16 , 1H-imidazole claim 16 , N-methyl-glucamine claim 16 , L-lysine claim 16 , choline claim 16 , L-arginine claim 16 , benethamine claim 16 , 4-(2-hydroxyethyl)-morpholine claim 16 , tromethamine claim 16 , 2-(dimethylamino) ethanol (Deanol) claim 16 , 1-(2-hydroxyethyl)-pyrrolidine claim 16 , 2-(diethylamino)-ethanol claim 16 , benzathine claim 16 , hydrabamine claim 16 , and betaine.20. The compound of formula IX according to claim 16 , wherein:{'sub': 1', '2', '1', '2, '(A) Ris C1-C6 alkyl, and Ris C1-C6 alkanediyl, and particularly Ris C1-C4 alkyl, and Ris C1-C4 alkanediyl; and/or'}{'sub': 1', '2, '(B) Ris C1 ...

CATALYSTS FOR CHEMICAL REACTIONS IN A WATER-SURFACTANT MIXTURE

The present invention is directed to reaction mixtures comprising a water-surfactant mixture, wherein the catalyst comprises a compound with solubilizing groups. This technology improves the solubility of the reaction components in the water-surfactant mixture and thereby, greatly increases the productivity and selectivity of the chemical reaction. 1. A reaction mixture comprising one or more reactants , a catalyst and a surfactant-water mixture , wherein the catalyst is(a) a coupling reagent comprising one or more solubilizing groups; or(b) a metal ion in complex with a ligand comprising one or more solubilizing groups;{'sub': '5-50', 'wherein the solubilizing group comprises a Calkyl group or a poly(alkylene glycol) group with 2 to 20 repeating units.'}2. The reaction mixture according to claim 1 , wherein the solubilizing group comprises a Calkyl group and has one or more of the following features:(i) the alkyl group is linear;(ii) the alkyl group comprises 8-15 carbon atoms, in particular 10-14 carbon atoms, especially 12 carbon atoms;(iii) it is substituted with one or more groups selected from methoxy, ethoxy, propoxy, hydroxy, amino optionally substituted with one or two of methyl, ethyl and/or propyl, in particular methoxy, ethoxy or hydroxy;(iv) it is 12-methoxydodecyl or dodecyl.3. The reaction mixture according to claim 1 , wherein the solubilizing group comprises a poly(alkylene glycol) group with 2 to 20 repeating units and has one or more of the following features:(i) the poly(alkylene glycol) group is a poly(ethylene glycol) group or poly(propylene glycol) group, in particular a poly(ethylene glycol) group;(ii) the poly(alkylene glycol) group has 3 to 8 repeating units, in particular 4 to 6 repeating units;(iii) it is substituted with one or more groups selected from methyl, ethyl, propyl, methoxy, ethoxy, propoxy, hydroxy, amino optionally substituted with one or two of methyl, ethyl and/or propyl, in particular methyl, ethyl or propyl;(iv) it is a ...

METHOD FOR SELECTIVELY SYNTHESIZING CATIONIC LIPIDS

Disclosed is a method capable of selectively synthesizing cationic lipids by controlling the introduction rate of a fatty acid group with respect to an oligoalkyleneamine by the change of reaction conditions. 2. The method for preparing a cationic lipid according to claim 1 , wherein the molar ratio of the oligoalkyleneamine to the fatty acid alkyl ester is adjusted to more than 1 to 20 or less to obtain the cationic lipid of Formula 1 where one of R1 and R4 is hydrogen and R2 and R3 are hydrogen.3. The method for preparing a cationic lipid according to claim 1 , wherein the molar ratio of the fatty acid alkyl ester to the oligoalkyleneamine is adjusted to 1 or more to 5 or less to obtain the cationic lipid of Formula 1 where R1 and R4 are independently saturated or unsaturated fatty acid groups having 12 to 26 carbon atoms and R2 and R3 are hydrogen.4. The method for preparing a cationic lipid according to claim 1 , wherein the molar ratio of the fatty acid alkyl ester to the oligoalkyleneamine is adjusted to more than 5 to 20 or less to obtain the cationic lipid of Formula 1 where R1 claim 1 , R2 claim 1 , R3 and R4 are independently saturated or unsaturated fatty acid group having 12 to 26 carbon atoms.5. A method for preparing a cationic lipid of Formula 1 of where R1 and R4 are saturated or unsaturated fatty acid group having 12 to 26 carbon atoms claim 1 , and one of R2 and R3 is hydrogen claim 1 , wherein the method comprises{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00001', 'claim 1'}], 'reacting the cationic lipid of Formula 1 defined in where R1 and R4 are saturated or unsaturated fatty acid group having 12 to 26 carbon atoms and R2 and R3 are hydrogen, with a fatty acid alkyl ester of Formula 3 defined in to prepare the cationic lipid of Formula 1 where R1 and R4 are saturated or unsaturated fatty acid group having 12 to 26 carbon atoms and one of R2 and R3 is hydrogen.'}6. The method for preparing a cationic lipid according to ...

MANUFACTURING PROCESS FOR MEMANTINE

A method for manufacturing 3,5-dimethyl-1-adamantanamine of the present invention comprises: (i) a step of reacting 3,5-dimethyl-1-adamantanol with an acid and nitrile in an organic solvent to obtain a reaction solution; (ii) a step of adding water to the reaction solution obtained in step (i) to obtain 1-amido-3,5-dimethyladamantane; and (iii) a step of hydrolyzing 1-amido-3,5-dimethyladamantane obtained in step (ii) in the presence of an alcohol-containing solvent and an inorganic base. 1. A method for manufacturing 3 ,5-dimethyl-1-adamantanamine , comprising:(i) a step of reacting 3,5-dimethyl-1-adamantanol with an acid and nitrile in an organic solvent to obtain a reaction solution;(ii) a step of adding water to the reaction solution obtained in step (i) to obtain 1-amido-3,5-dimethyladamantane; and(iii) a step of hydrolyzing 1-amido-3,5-dimethyladamantane obtained in step (ii) in the presence of an alcohol-containing solvent and an inorganic base.2. The method according to claim 1 , wherein the organic solvent used in step (i) is hydrophobic.3. The method according to claim 1 , wherein the organic solvent used in step (i) contains at least one organic solvent selected from the group consisting of an aliphatic hydrocarbon and an aromatic hydrocarbon.4. The method according to claim 1 , wherein the alcohol-containing solvent used in step (iii) contains at least one alcohol selected from monovalent linear primary alcohols.5. The method according to claim 1 , wherein the alcohol-containing solvent used in step (iii) contains at least one alcohol selected from the group consisting of 1-butanol claim 1 , 1-pentanol claim 1 , 1-hexanol claim 1 , 1-heptanol claim 1 , and 1-octanol.6. The method according to claim 1 , wherein a molar ratio of the acid to 3 claim 1 ,5-dimethyl-1-adamantanol in step (i) is 1 to 10.7. The method according to claim 1 , wherein a molar ratio of the nitrile to 3 claim 1 ,5-dimethyl-1-adamantanol in step (i) is 1 to 10.8. The method according ...

METHOD FOR PREPARING PREGABALIN INTERMEDIATE 3-CARBAMOYMETHYL-5-METHYLHEXANOIC ACID WITHOUT SOLVENT

The present invention provides a method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent. The method comprises the following steps: a) cooling an ammonia water system to a certain temperature; b) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting; c) after completing the reaction, adding an acid to the system to adjust pH; d) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and e) adding a solvent to the dried substance, slurrying, and suction filtering and drying to obtain the final product. The method provided in the present invention for preparing 3-carbamoymethyl-5-methylhexanoic acid is high-yield, green, environmentally-friendly, simple and convenient, and of less pollution. 1. A method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent , characterized in that the method comprises the following steps:1) cooling an ammonia water system to a certain temperature;2) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting;3) after completing the reaction, adding an acid to the system to adjust pH;4) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and5) adding a solvent to the dried substance, slurrying, suction filtering and drying to obtain the final product.2. The method according to claim 1 , characterized in that the certain temperature of step 1) is 0 to 20° C. claim 1 , and the amount of the ammonia water used by weight is 0.9 to 1.1 times of the weight of 3-isobutylglutaric anhydride.3. The method according to claim 1 , characterized in that the duration for keeping temperature and reacting is 2 to 4 h in step 2).4. The method according to claim 1 , characterized in that the pH is adjusted in the range of 2 to 4 in step 3).5. The method according to claim 1 , ...

PREPARATION OF N,N-(DI)ALKYLAMINOALKYL(METH)ACRYLAMIDE OR N,N-(DI)ALKYLAMINOALKYL (METH)ACRYLATE AND THE QUATERNARY AMMONIUM SALTS THEREOF AS FLOCCULATING AIDS AND GELLING AGENTS

N,N-(di)alkylaminoalkyl(meth)acrylamide or N,N-(di)alkylaminoalkyl (meth)acrylate and/or a quaternary ammonium salt thereof are prepared with a low content of a compound of formula (IV) 2. The process for preparing N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 1 , wherein the N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate or quaternary ammonium salts thereof have a content of less than 1200 ppm of the compound of the formula (IV) and are suitable for preparation of a soluble or non-coagulating polymer.3. The process for preparing N claim 2 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 2 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 2 , wherein the N claim 2 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 2 ,N-(di)alkylaminoalkyl (meth)acrylate or quaternary ammonium salts thereof have a content of less than 1000 ppm of the compound of the formula (IV).4. The process for preparing N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 1 , wherein the preparing is effected with exclusion of oxygen.5. The process for preparing N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 1 , wherein the preparing is conducted under a protective gas atmosphere.6. The process for preparing N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 1 , wherein a residence time is 0.1-11 h.7. The process for preparing N claim 1 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 1 ,N-(di)alkylaminoalkyl (meth)acrylate according to claim 1 , wherein the preparing is conducted at temperatures between 70° C. and 160° C.8. The process for preparing N claim 6 ,N-(di)alkylaminoalkyl(meth)acrylamide or N claim 6 ,N-(di)alkylaminoalkyl (meth)acrylate according to ...

IOHEXOL PRODUCTION PROCEDURE.

EL PROCEDIMIENTO SUMINISTRA UN PROCESO PARA LA PRODUCCION DE IOHEXOL (FORMULA I) QUE COMPRENDE LA REACCION DE 5-ACETAMIDO-N, N''-BIS(2,3-DIHIDROXIPROPIL)-2,4,6-TRIIODOFTALAMIDA CON UN AGENTE 2,3-DIHIDROXIPROPILANTE, LA MEJORA COMPRENDE LA REALIZACION DEL PROCESO EN LA PRESENCIA DE UN SOLVENTE QUE COMPRENDE 2-METOXIETANOL Y, OPCIONALMENTE, ISOPROPANOL. THE PROCEDURE PROVIDES A PROCESS FOR THE PRODUCTION OF IOHEXOL (FORMULA I) THAT INCLUDES THE REACTION OF 5-ACETAMID-N, N '' - BIS (2,3-DIHYDROXIPROPIL) -2,4,6-TRIIODOFTALAMIDE WITH AN AGENT 2, 3-DIHYDROXIPROPILANT, THE IMPROVEMENT UNDERSTANDS THE PERFORMANCE OF THE PROCESS IN THE PRESENCE OF A SOLVENT THAT INCLUDES 2-METOXYETHANOL AND, OPTIONALLY, ISOPROPANOL.

PROCESS FOR MANUFACTURE OF AMANTADINE NITRATE DERIVATIVES

The present invention provided a process for manufacture of amantadine nitrate derivatives, and the process comprises using adamantane as the raw material to prepare amantadine nitrate derivatives via the following steps: (1) synthesis of adamantanol; (2) carboxylation of adamantanol; (3) acetylation of adamantanoic acid; (4) reduction; (5) hydrolysis of amido adamantanol and Boc protection of amino group; (6) crystallization of Boc protected amantadinol; (7) nitrate esterification of Boc protected amantadinol; (8) refining of the product of nitrate esterification; (9) Boc deprotection and salt formation; and (10) refining of amantadine nitrate hydrochloride. The amantadine nitrate derivatives have the struction of: 2. (canceled)3. The process according to claim 1 , wherein step (1) further comprises:(1a) Bromination: reacting a substituted or unsubstituted adamantane with liquid bromine in reflux for 4-6 h to obtain bromoadamantane; and(1b) Hydrolysis: adding sodium oxalate and water, the reaction system being refluxed at 75° C. via hydrolization to obtain a substituted or unsubstituted adamantanol.4. The process according to claim 1 , wherein step (2) further comprises: the product from step (1) being dissolved in formic acid claim 1 , and slowly added dropwise to concentrated sulfuric acid with cooling to 0-10° C. claim 1 , and then the reaction being maintained at 0-10° C. for 3-6 h; the reaction solution being poured into ice water and stirred for 16-18 h; after suction filtration claim 1 , the solid filter cake being washed with water claim 1 , dissolved with 0.27× sodium hydroxide solution claim 1 , and filtered with suction; the filtrate being acidified with 5-10% hydrochloric acid to pH=1-2 and filtered claim 1 , the filter cake being washed with water until the filtrate being neutral claim 1 , and dried at 40-50° C. to obtain adamantanoic acid.5. The process according to claim 1 , wherein step (3) further comprises: cooling concentrated sulfuric acid to 0- ...

Processo

Process for preparing acrylamide

Chemical process.

METHOD FOR PRODUCING N-ALKANOYL-POLYHYDROXYALKYLAMINES

Chemical process

요오헥솔의 제조 방법

본 발명은 5-아세트아미도-N,N'-비스(2,3-디히드록시프로필)-2,4,6-트리요오도프탈아미드를 2,3-디히드록시프로필화제와 반응시키는 것을 포함하는 요오헥솔(화학식 1)의 제조 방법에 있어서, 상기 반응을 2-메톡시-에탄올 및 임의로는 이소프로판올을 포함하는 용매의 존재하에 수행하는 것을 특징으로 하는 요오헥솔의 제조 방법에 관한 것이다.

Process for the Preparation of Contrast Agents

본 발명은 상응하는 아미노-페닐-카르복실산(또는 카르복실산 유도체)의 액상 아실화 및 후속 N-알킬화에 의한 N-알킬-아실아미노-페닐-카르복실산 또는 카르복실산 유도체의 제조 방법에 있어서, 상기 아실화 반응 생성물을 함유하는 용액에 알킬화제를 첨가하여 상기 N-알킬화를 수행하는 것을 특징으로 하는 N-알킬-아실아미노-페닐-카르복실산 또는 카르복실산 유도체의 제조 방법에 관한 것이다. The present invention provides a process for the preparation of N-alkyl-acylamino-phenyl-carboxylic acids or carboxylic acid derivatives by liquid acylation of the corresponding amino-phenyl-carboxylic acids (or carboxylic acid derivatives) and subsequent N-alkylation. A process for producing an N-alkyl-acylamino-phenyl-carboxylic acid or carboxylic acid derivative, wherein the N-alkylation is carried out by adding an alkylating agent to a solution containing the acylation reaction product. will be.

Processo para a produção de uma hidroxialamida

Process for preparing ß-hydroxyalkylamides.

一种依非韦伦关键中间体的合成方法

本发明提供一种依非韦伦关键中间体的合成方法，包括以下步骤：将对氯苯胺与特戊酰氯反应保护氨基得N‑(4‑氯苯基)‑2,2‑二甲基丙酰胺；上述产物和三氟乙酸酐在三氯化铝作用下经傅‑克酰基化反应后，在酸性条件下水解得4‑氯‑2‑三氟乙酰基苯胺盐酸盐；然后经碱化得4‑氯‑2‑三氟乙酰基苯胺，与配体(1R,2S)‑1‑苯基‑2‑(1‑吡咯烷基)‑1‑丙醇形成的催化体系中与环丙乙炔氯化镁反应，经不对称自催化反应制得依非韦伦关键中间体。本发明提供的依非韦伦关键中间体的合成方法，原料价廉易得，所用试剂毒性低，反应条件温和，不需要频繁地进行氨基保护和脱保护，路线简洁，各步反应收率优良，总收率高。

Process