Method for preparing polyamine compounds

A method for preparing a compound having formula (II) wherein R 1 and R 2 independently are methyl or ethyl, or R 1 and R 2 combine to form a C 5 or C 6 cycloalkyl or cycloalkenyl group. The method includes a step of combining R 1 R 2 CHNO 2 , glutaraldehyde and an amine. The compound is useful in coating compositions and other applications for pH adjustment.

ASYMMETRIC CYCLIZATION PROCESSES USING UNSATURATED NITRO COMPOUNDS

Disclosed are processes of forming a compound (33), (35) or (37) 2. The process of claim 1 , further comprising contacting the compound of general formula (23) with a compound of general formula R—X claim 1 , wherein X is one of H claim 1 , halogen claim 1 , —CN claim 1 , —COOR claim 1 , —COSR—COSeRand —CONRRwherein Ris one of halogen claim 1 , —CN claim 1 , an aliphatic claim 1 , an alicyclic claim 1 , an aromatic claim 1 , an arylaliphatic claim 1 , and an arylalicyclic group with a main chain of a length of 1 to about 20 carbon atoms claim 1 , comprising 0 to about 6 heteroatoms selected from the group consisting of N claim 1 , O claim 1 , S claim 1 , Se and Si claim 1 , and Rand Rare independent from one another one of H claim 1 , an aliphatic claim 1 , an alicyclic claim 1 , an aromatic claim 1 , an arylaliphatic claim 1 , and an arylalicyclic group with a main chain of a length of 1 to about 20 carbon atoms claim 1 , comprising 0 to about 6 heteroatoms selected from the group consisting of N claim 1 , O claim 1 , S claim 1 , Se and Si claim 1 , thereby allowing the formation of a compound of general formula (33).3. The process of claim 1 , wherein the compound of general formula (X) is present in a catalytical amount.4. The process of claim 1 , wherein the process is carried out in a solvent.5. The process of claim 1 , wherein contacting the first compound of formula (1) and the second compound of formula (2) is carried out at a temperature selected in the range from about −40° C. to about 40° C.6. The process of claim 5 , wherein contacting the first compound of formula (1) and the second compound of formula (2) is carried out at ambient temperature.923-. (canceled)24. The process of claim 4 , wherein the process is carried out in a polar liquid.25. The process of claim 4 , wherein the process is carried out in a non-polar liquid. This application is a continuation of the U.S. application Ser. No. 12/782,704, filed May 18, 2010, which in turn makes reference ...

Fragmentation Reagents For Mass Spectrometry

A mass spectrometry electron transfer dissociation reagent comprising an unsaturated compound having a Frank Condon factor between 0.1 and 1.0 and an electron affinity having a positive value between 0.1 to 150 kJ/mol. 1. A mass spectrometry electron transfer dissociation reagent comprising an unsaturated compound having a Frank Condon factor between 0.1 and 1.0 and an electron affinity having a positive value between 0.1 to 200 kJ/mol.2. The reagent of claim 1 , wherein the unsaturated compound is a substituted aromatic or conjugated aliphatic compound.3. The reagent of claim 1 , wherein the electron affinity has a positive value between 0.1 to 150 kJ/mol claim 1 , preferably 0.1 to 100 kJ/mol.4. The reagent of claim 1 , wherein the unsaturated compound is an aromatic compound claim 1 , wherein the nucleus of the aromatic compound is substituted with one or more substituents consisting of cyano claim 1 , nitro claim 1 , nitroso claim 1 , carboxyl claim 1 , iodo claim 1 , aldehyde and acetoxy.5. The reagent of claim 4 , wherein the one or more substituents are cyano.6. The reagent of claim 4 , wherein the nucleus is selected from the group consisting of phenyl claim 4 , pyridinyl claim 4 , pyrimidinyl claim 4 , triazolyl claim 4 , styrenyl and picolinyl.7. The reagent of claim 1 , wherein the unsaturated compound is an unsaturated aliphatic compound selected from the group consisting of ethylene claim 1 , acetylene or acrylate substituted with one or more substituents.8. The reagent of claim 7 , wherein two or more unsaturated bonds are conjugated.9. The reagent of claim 7 , wherein the unsaturated aliphatic compound is selected from the group consisting of ethylene claim 7 , acetylene or acrylate substituted with one or more unsaturated groups selected from the group consisting off cyano claim 7 , nitro claim 7 , aceto claim 7 , carboxyl claim 7 , aldehyde and nitroso.10. The reagent of selected from the group consisting of 1 claim 1 ,4-dicyanobenzene claim 1 , 1 ...

NOVEL PROCESS FOR PREPARING PHENYLCYCLOPROPYLAMINE DERIVATIVES USING NOVEL INTERMEDIATES

Provided herein is a novel process for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein is a novel, commercially viable and industrially advantageous process for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. The intermediate is useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity. 2. The process of claim 1 , wherein the halogen atom in the compounds of formulae II claim 1 , III claim 1 , IV claim 1 , V claim 1 , VI and VII is F; and wherein the leaving group ‘X’ in the compound of formula VIII is Cl.3. The process of claim 1 , wherein the R claim 1 , Rand Rin the compounds of formulae II claim 1 , III claim 1 , IV claim 1 , V claim 1 , VI and VII are H claim 1 , and wherein the Rand Rare F.4. The process of claim 1 , wherein the first solvent used in step-(a) is selected from the group consisting of an aliphatic or alicyclic hydrocarbon claim 1 , a chlorinated aliphatic or aromatic hydrocarbon claim 1 , an aromatic mono or dinitro hydrocarbon claim 1 , and mixtures thereof; wherein the second solvent used in step-(b) is selected from the group consisting of a ketone claim 1 , an aliphatic amide claim 1 , a nitrile claim 1 , a hydrocarbon claim 1 , a cyclic ether claim 1 , an aliphatic ether claim 1 , a polar aprotic solvent claim 1 , and mixtures thereof; wherein the third solvent used in step-(c) is selected from the group consisting of a hydrocarbon claim 1 , a cyclic ether claim 1 , an aliphatic ether claim 1 , a chlorinated hydrocarbon claim 1 , and mixtures thereof; wherein the fourth solvent used in step-(d) is selected from the group consisting of a hydrocarbon claim 1 , cyclic ethers claim 1 , an ether claim 1 , an ester claim 1 , a nitrile claim 1 , an aliphatic amide claim 1 , a chlorinated hydrocarbon claim 1 ...

TREATMENT OF MITOCHONDRIAL DISEASES WITH NAPHTHOQUINONES

Methods of treating, preventing or suppressing symptoms associated with mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), dominant optic atrophy (DOA); mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Leigh syndrome or Kearns-Sayre Syndrome (KSS) with compounds of Formula (I) are disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods are also disclosed. 3. The method according to claim 1 , wherein R claim 1 , Rand Rare independently selected from —(C-C)alkyl.4. The method according to claim 1 , wherein Rand Rare hydrogen and Ris —(C-C)alkyl.5. The method according to claim 1 , wherein Rand Rare independently of each other —O(C-C)alkyl and Ris —(C-C)alkyl.7. The method according to claim 6 , wherein R claim 6 , Rand Rare independently of each other —(C-C)alkyl.8. The method according to claim 6 , wherein Rand Rare —O(C-C)alkyl and Ris —(C-C)alkyl.9. The method according to claim 6 , wherein the bond indicated by a dashed line is a double bond.10. The method according to claim 6 , wherein the bond indicated by a dashed line is a single bond.12. The method according to claim 11 , wherein R claim 11 , Rand Rare independently of each other —(C-C)alkyl.13. The method according to claim 11 , wherein Rand Rare hydrogen and Ris —(C-C)alkyl.14. The method according to claim 11 , wherein Rand Rare —O(C-C)alkyl and Ris —(C-C)alkyl.15. The method according to claim 11 , wherein the bond indicated by a dashed line is a double bond.16. The method according to claim 11 , wherein the m′ is 3.17. The method according to claim 11 , wherein the compound is selected from:2-(3-hydroxy-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yl)-3-methylnaphthalene-1,4-dione;2-(3-hydroxy-3,7,11,15-tetramethylhexadeca-6,10,14-trien-1-yl)naphthalene-1,4-dione; and any stereoisomer, mixture of stereoisomers, salt, crystalline form, non-crystalline form, hydrate ...

Process for producing ester compound

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

SMALL MOLECULE XANTHINE OXIDASE INHIBITORS AND METHODS OF USE

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled) This application claims priority to U.S. Provisional Application No. 61/734,409, filed Dec. 7, 2012, which is incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then catalyzes the oxidation of xanthine to uric acid. Meanwhile, reactive oxygen species (ROS), including superoxide and HO, are generated during this process. Uric acid can serve as an antioxidant to prevent macromolecular damage by ROS. However, overproduction of uric acid can cause hyperuricemia and lead to gout and other diseases. Therefore, maintaining uric acid at normal levels represents an important therapeutic goal for the prevention of gout and related disorders. For most patients with primary gout, overproduction of uric acid is the primary cause of hyperuricemia.Currently, two drugs have been developed to treat gout. Allopurinol is the most commonly used therapy for chronic gout and has been used clinically for more than 40 years. Allopurinol lowers uric acid production by inhibiting XO activity, and is used as a first-line urate-lowering phamacotherapy. Allopurinol, ...

Small Molecule Xanthine Oxidase Inhibitors and Methods of Use

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled)18. The method of claim 16 , wherein the compound is administered orally. This application claims priority to U.S. Provisional Application No. 61/734,409, filed Dec. 7, 2012, which is incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then catalyzes the oxidation of xanthine to uric acid. Meanwhile, reactive oxygen species (ROS), including superoxide and HO, are generated during this process. Uric acid can serve as an antioxidant to prevent macromolecular damage by ROS. However, overproduction of uric acid can cause hyperuricemia and lead to gout and other diseases. Therefore, maintaining uric acid at normal levels represents an important therapeutic goal for the prevention of gout and related disorders. For most patients with primary gout, overproduction of uric acid is the primary cause of hyperuricemia.Currently, two drugs have been developed to treat gout. Allopurinol is the most commonly used therapy for chronic gout and has been used clinically for more than 40 years. Allopurinol lowers uric acid production by inhibiting XO activity, ...

Methods for the synthesis of activated ethylfumarates and their use as intermediates

Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput. 2. The method of claim 1 , wherein the organic solvent is selected from acetone claim 1 , acetonitrile claim 1 , ethyl acetate claim 1 , tetrahydrofuran claim 1 , and dichloromethane.3. The method of claim 1 , wherein the inorganic metallic base is selected from sodium carbonate and sodium hydroxide.4. The method of claim 1 , wherein the base is provided in an amount of 1 to 2 equivalents based on the amount of 4-nitrophenol.5. The method of claim 1 , wherein the ethyl fumaryl chloride is provided in an amount of 0.5 to 2 equivalents based on the amount of 4-nitrophenol.6. The method of claim 1 , wherein the inorganic metallic base is added as an aqueous mixture to a solution of 4-nitrophenol in the organic solvent.7. The method of claim 1 , wherein the ethyl fumaryl chloride is added to a mixture of 4-nitrophenol and the inorganic metallic base claim 1 , with cooling.8. The method of claim 1 , wherein the aminoalkyl-diketopiperazine is mixed with an organic solvent to form an aminoalkyl-diketopiperazine-containing mixture prior to adding the aminoalkyl-diketopiperazine.9. The method of claim 8 , wherein the organic solvent in the aminoalkyl-diketopiperazine-containing mixture is the same organic solvent used to form the mono-ethyl fumarate ester.10. The method of claim 8 , wherein the ...

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF NEP INHIBITORS

The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route. 7. The process according to claim 6 , comprising the step of simultaneously or separately esterifiying the obtained compound of formula (1) claim 6 , or a salt thereof claim 6 , wherein R1 is hydrogen claim 6 , with a C-C-aliphatic alcohol claim 6 , to yield the compound of formula (1) wherein R1 is C-C-alkyl.15. (canceled)19. (canceled)21. (canceled)24. (canceled) The present invention relates to a new chemical synthesis route and intermediates useful for the preparation of neprilysin (NEP) inhibitors and their prodrugs, in particular for the NEP inhibitor prodrug sacubitril.The NEP inhibitor prodrug sacubitril (N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester; IUPAC name 4-{[(1S,3R)-1-([1,1′-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoic acid) is represented by the following formula (A)Sacubitril together with valsartan, a known angiotensin receptor blocker (ARB), forms a sodium salt hydrate complex, known as LCZ696, comprising the anionic forms of sacubitril and valsartan, sodium cations and water molecules in the molar ratio of 1:1:3:2.5, respectively (ratio of 6:6:18:15 in the asymmetric unit cell of the solid state crystal), and which is schematically present in formula (B).Said complex is also referred to by the following chemical names: Trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3′-methyl-2′-(pentanoyl{2″-(tetrazol-5-ylate)biphenyl-4′-ylmethyl}amino)butyrate] hemipentahydrate or Octadecasodium hexakis(4-{[(1S,3R)-1-([1,1′-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoate) hexakis(N-pentanoyl-N-{[2′-(1H-tetrazol-1-id-5-yl)[1,1′-biphenyl]-4-yl]methyl}-L- ...

PHOSPHINE SUBSTITUTED FERROCENYL COMPLEX

A functionalized magnetic nanoparticle including an organometallic sandwich compound and a magnetic metal oxide. The functionalized magnetic nanoparticle may be reacted with a metal precursor to fol in a catalyst for various C—C bond forming reactions. The catalyst may be recovered with ease by attracting the catalyst with a magnet. 2. (canceled)3. The complex of claim 1 , wherein Ris an optionally substituted alkyl.4. The complex of claim 1 , wherein Ris an optionally substituted aryl.5. The complex of claim 1 , wherein X is NH.620-. (canceled) This application claims the priority of the filing date of the U.S. Provisional Patent Application No. 62/406,449 filed Oct. 11, 2016, the disclosure of which is hereby incorporated herein by reference in its entirety.This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH)-King Abdulaziz City for Science and Technology through the Science and Technology Unit at King Fahd University of Petroleum and Minerals (KFUPM), the Kingdom of Saudi Arabia, award number 15-NAN4650-04.Aspects of this technology are described in an article “Magnetic nanoparticle-supported ferrocenylphosphine: a reusable catalyst for hydroformylation of alkene and Mizoroki-Heck olefination” by M. Nasiruzzaman Shaikh, Md. Abdul Aziz, Aasif Helal, Mohamed Bououdina, Zain H. Yamania, and Tae-Jeong Kim, in RSC Advances, 2016, pages 41687-41695, which is incorporated herein by reference in its entirety.The present disclosure relates to a functionalized magnetic nanoparticle including an organometallic sandwich compound and a functional group which can bind to a nanoparticle. The disclosure also relates to a magnetic catalyst which catalyzes C—C bond forming reactions such as hydroformylation and the Mizoroki-Heck coupling reaction.Carbon-carbon bond formation reactions mediated by various transition metals have emerged as increasingly important methodologies for the preparation of numerous organic building blocks for drugs, ...

Process for the Preparation of Nitroalcohols

A process of preparing a nitroalcohol, e.g., 2-nitro-2-methyl-1-propane, from a nitropolyol, e.g., 2-nitro-2 -methyl-1,3-propanediol, the process comprising the step of contacting under hydrogenation conditions the nitropolyol with hydrogen, a hydrogenation catalyst and, optionally, a chelating agent. 1. A process of preparing a nitroalcohol from a nitropolyol , the process comprising the step of contacting at a temperature of 25-120° C. and a pressure of 300-1400 psi a nitropolyol with hydrogen and a hydrogenation catalyst , wherein the hydrogenation catalyst is at least one of a platinum group metal or a precious metal.2. (canceled)3. (canceled)4. The process of in which the hydrogenation catalyst is used in combination with a chelating agent.5. The process of in which the chelating agent is at least one of diethylenetriaminiepentaacetic acid (DTPA) claim 4 , ethylenediaminetetraacetic acid (EDTA) claim 4 , N claim 4 ,N′-bis(2-hydroxyethyl)ethylenediamine-N claim 4 ,N′-diacetic acid (HEEDA) claim 4 , N-2-hydroxyethyl-iminodiacetic acid (HEIDA) and nitrilotriacetic acid (NTA).6. The process of in which the amount of chelating agent used on a weight to weight basis with the catalyst metal is 1:1 to 1.5:1.7. The process of in which the nitropolyol is at least one of 2-nitro-2-methyl-1 claim 6 ,3-propanediol and tris(hydroxymethyl)nitromethane.8. A process of preparing a nitroalcohol from a nitroalkane claim 6 , the process comprising the steps of:A. Contacting under alkaline conditions a nitroalkane, an alcohol aldehyde and an alkaline catalyst to form a nitropolyol, andB. Contacting at a temperature of 25-120° C. and a pressure of 300-1400 psi the nitropolyol of A with hydrogen, a hydrogenation catalyst and, optionally, a chelating agent, wherein the hydrogenation catalyst is at least one of a platinum group metal or a precious metal. 1. Field of the InventionThis invention relates to a process of producing nitroalcohols by the reductive dehydroxylation of ...

SYNTHESIS OF (2-NITRO)ALKYL (METH)ACRYLATES VIA TRANSESTERIFICATION OF (METH)ACRYLATE ESTERS

Provided is a process for making (2-nitro)alkyl (meth)acrylate compounds of formula I: wherein n, R, R, R, R, R, R, R, and n are as defined herein, by a transesterification reaction between a nitroalcohol compound and a (meth)acrylate compound in the presence of a transesterification catalyst and a free radical inhibitor. 2. The process of wherein the transesterification catalyst is dibutyltin oxide claim 1 , a zirconium complex claim 1 , a hafnium complex claim 1 , a tetra-alkoxy titanate claim 1 , lithium hydroxide claim 1 , barium oxide claim 1 , magnesium oxide claim 1 , strontium oxide claim 1 , calcium oxide claim 1 , magnesium methylate claim 1 , 1 claim 1 ,4-diazabicyclo[2.2.2]octane claim 1 , a basic ion exchange resin claim 1 , or a mixture of two or more thereof.3. The process of wherein the transesterification catalyst is dibutyltin oxide claim 1 , a zirconium complex claim 1 , a hafnium complex claim 1 , 1 claim 1 ,4-diazabicyclo[2.2.2]octane claim 1 , or a mixture of two or more thereof.4. The process of wherein the transesterification catalyst is a zirconium complex.5. The process of wherein the mole ratio of (meth)acrylate compound to nitroalcohol is from 1:1 to 20:1.6. The process of wherein excess (meth)acrylate and its corresponding alcohol form an azeotropic mixture and wherein this byproduct alcohol is removed by azeotropic distillation.7. The process of wherein the free-radical inhibitor is claim 1 , phenothiazine claim 1 , hydroquinone claim 1 , methyl ether of hydroquinone claim 1 , 4-Hydroxy-TEMPO claim 1 , or mixtures thereof.8. The process of wherein Ris H and Ris H or linear or branched C-Calkyl optionally substituted with NO.9. The process of wherein Rand R′ are independently linear or branched C-Calkyl claim 1 , or Rand R′ claim 1 , together with the carbon atom to which they are attached claim 1 , form C-Ccycloalkyl.10. The process of wherein the compound of formula I is: 2-methyl-2-nitropropyl acrylate; 2-methyl-2-nitropropyl ...

1,3-DI-OXO-INDENE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT OR OPTICAL ISOMER THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS AN ANTIVIRAL, ACTIVE INGREDIENT

Disclosed are 1,3-Dioxoindene derivatives, pharmaceutically acceptable salts thereof or enantiomers, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of viral diseases, comprising the same as an active ingredient. The 1,3-Dioxoindene derivatives have excellent inhibitory activity against picornaviruses including coxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well as exhibiting low cytotoxicity, so that they can be useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of viral diseases including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, flu, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media. 3. The 1 claim 1 ,3-Dioxoindene derivatives claim 1 , pharmaceutically-acceptable salt thereof or optical isomer thereof as set forth in claim 1 , wherein claim 1 , A claim 1 , A claim 1 , Aand Aare claim 1 , either independently or optionally claim 1 , any one selected from a group consisting of —H claim 1 , halogen and —NRR;{'sup': 1', '2', '1', '2, 'G is —OH, —NR(C═O)Ror —NR(C═O)OR;'}{'sup': 1', '2', '3', '4', '1', '2, 'sub': 1', '10, 'D, D, Dand Dare, either independently or optionally, any one selected from a group consisting of halogen, C˜Cstraight- or side-chain alkyl and —NR(C═O)R;'}{'sup': 1', '1', '1', '1', '2, 'E is —H, —OH, —OR, —O(C═O)R, —O(C═O)ORor —O(C═O)NRR;'}{'sup': 1', '2', '3, 'sub': 1', '8', '1', '4', '6', '10, 'R, Rand Rare, each independently, hydrogen, nonsubstituted or phenyl-substituted C˜Cstraight- or side-chain alkyl, nonsubstituted or phenyl-substituted C˜Cstraight- or side-chain alkenyl or C˜Caryl;'}X and Y are oxygen;{'sup': 1', '2', '3, 'Z, Zand Zare carbon;'}n is integer between 1˜3; and{'img': {'@id': 'CUSTOM- ...

METHOD FOR PRODUCING 1,1'-BINAPHTHYL DERIVATIVES AND 1,1'-BINAPHTHYL DERIVATIVES

In a production method of the present disclosure, a 1,1′-binaphthyl precursor derivative, an organic acid, and an iodinating or brominating agent are mixed. The 1,1′-binaphthyl precursor derivative has a 1,1′-binaphthyl skeleton and has an electron-donating group at the 2-position of the 1,1′-binaphthyl skeleton and at the 2′-position of the 1,1′-binaphthyl skeleton, and the electron-donating group contains an oxygen atom directly bonded to the skeleton. With the production method of the present disclosure, a 1,1′-binaphthyl derivative having a substituent introduced at the 8-position and/or 8′-position of the 1,1′-binaphthyl skeleton can be obtained. The 1,1′-binaphthyl derivative obtained by the production method of the present disclosure can be a compound further having a substituent introduced at at least one position selected from the 4-position, 4′-position, 5-position, 5′-position, 6-position, and 6′-position of the 1,1′-binaphthyl skeleton. 1. A method for producing 1 ,1′-binaphthyl derivatives , comprising mixing a 1 ,1′-binaphthyl precursor derivative , an organic acid , and an iodinating or brominating agent to obtain a 1 ,1′-binaphthyl derivative ,the 1,1′-binaphthyl precursor derivative having a 1,1′-binaphthyl skeleton and having an electron-donating group at 2-position of the skeleton and at 2′-position of the skeleton, the electron-donating group containing an oxygen atom directly bonded to the skeleton,the 1,1′-binaphthyl derivative having a substituent introduced at 8-position and/or 8′-position of the skeleton.2. The method for producing 1 claim 1 ,1′-binaphthyl derivatives according to claim 1 , wherein the precursor derivative claim 1 , the organic acid claim 1 , and the iodinating agent are mixed.3. The method for producing 1 claim 1 ,1′-binaphthyl derivatives according to claim 1 , wherein the electron-donating group is —OR wherein R is a hydrogen atom claim 1 , an alkyl group having 1 to 50 carbon atoms claim 1 , an allyl group claim 1 , a ...

Process for preparation of 2-amino-5-hydroxy propiophenone

The present invention relates to a process for preparation of 2-Amino-5-hydroxy propiophenone, a key intermediate for the synthesis of camptothecin analogs including 7-Ethyl-10-hydroxycamptothecin (SN-38).

PROCESS TO PREPARE 3-METHYL-2-NITROBENZOIC ACID BY AIR OXIDATION

A method for preparing 3-methyl-2-nitrobenzoic acid is disclosed wherein 1,3-dimethyl-2-nitrobenzene is combined with an oxidation catalayst in the presence of an oxygen source and an initiator, provided that less than 99% of the 1,3-dimethyl-2-nitrobenzene is oxidized. 2. The method of wherein Ris C-Calkyl or C-Ccycloalkyl.3. The method of wherein Ris methyl claim 2 , isopropyl claim 2 , cyclopropyl or t-butyl.4. The method of wherein Ris methyl or t-butyl.5. The method of wherein Ris C-Calkyl.6. The method of wherein Ris methyl or ethyl.7. The method of wherein Ris ethyl.8. The method of wherein the cyclizing agent is PBr.9. The method of wherein the chlorinating agent is HCl and HO.11. The method of wherein Ris C-Calkyl or C-Ccycloalkyl.12. The method of wherein Ris methyl claim 11 , isopropyl claim 11 , cyclopropyl or t-butyl.13. The method of wherein Ris methyl or t-butyl.14. The method of wherein Ris methyl.15. The method of wherein Ris t-butyl. A need exists for additional methods to prepare 3-methyl-2-nitrobenzoic acid that are selective and cost-effiective. 3-Methyl-2-nitrobenzoic acid is useful as in intermediate in the preparation of agrochemicals such as Rynaxypyr® and Cyazypyr®.Oxidation of mono-alkyl ortho-nitroalkylaromatic compounds is exemplified in Jacobsen, U.S. Pat. No. 5,591,890. Selective oxidation of one alkyl group in ortho-nitroalkylaromatic compounds with two or more alkyl groups is not disclosed in this patent.Oxidation of 2-nitro-p-xylene is disclosed in Jacobson and Ely, 1996, 68, 87-96. Selective oxidation of one alkyl group in ortho-nitroalkylaromatic compounds with two or more alkyl groups is not disclosed in this publication.Oxidation of 2-nitro-m-xylene is disclosed in JP05132450 using HSOand stoichiometric CrO.This invention provides a method for preparing a compound of Formula 2comprising, contacting a compound of Formula 1with an oxidation catalyst in the presence of an oxygen source and an initiator provided that less than 99% ...

Small Molecule Xanthine Oxidase Inhibitors and Methods of Use

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 3. The method of claim 1 , further comprising administering a second therapeutic agent to the subject.4. The method of claim 3 , wherein the second therapeutic agent is an anti-gout agent.5. The method of claim 4 , wherein the anti-gout agent is selected from the group consisting of allopurinol claim 4 , benzbromarone claim 4 , colchicine claim 4 , probenecid claim 4 , and sulfinpyrazone.6. The method of claim 3 , wherein the second therapeutic agent is an anti-inflammatory agent.7. The method of claim 3 , wherein the second therapeutic agent is an antioxidant.8. The method of claim 1 , wherein the compound is administered orally.11. The method of claim 9 , wherein the method further comprises selecting a subject having gout or hyperuricemia.14. The method of claim 12 , wherein the contacting is performed in vivo.15. The method of claim 12 , wherein the contacting is performed in vitro. This application claims priority to U.S. Provisional Application No. 61/734,409, filed Dec. 7, 2012, which is incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then ...

TRIPHASIC FLOW MILLIREACTORS

Disclosed is a reactor system that contains multiple millireactors, each including a millitube, a first feed line, a second feed line, and a third feed line. Each of the first and second feed lines has a hydraulic damper disposed therein. Also disclosed is a process for conducting in a millitube a triphasic flow reaction that requires a liquid reactant, a gas reactant, and a catalyst. 2. The reactor system of claim 1 , further comprising:a first liquid container connected to the first end of the first feed line, the first container connected in fluid communication to a first pump;a second liquid container connected to the first end of the second feed line, the second container connected in fluid communication to a second pump;a gas container connected to the first end of the third feed line; andan outflow container connected to the second end of the millitube.3. The reactor system of claim 2 , wherein the first and second pumps are each a peristaltic pump.4. The reactor system of claim 1 , wherein the millitube is a polytetrafluoroethylene tube.5. The reactor system of claim 4 , wherein the millitube has a length of 2-20 m and an inner diameter of 1-5 mm.6. The reactor system of claim 4 , wherein the first and second hydraulic dampers each consist of a first tube claim 4 , a second tube claim 4 , and a third tube in series claim 4 , the second tube having an inner diameter larger than that of the first tube and that of the third tube.7. The reactor system of claim 6 , wherein the first tube has the same length and inner diameter as those of the third tube.8. The reactor system of claim 6 , wherein the second tube in the first hydraulic damper is a silicone tube and the second tube in the second hydraulic damper is a viton tube.9. The reactor system of claim 5 , wherein the first and second hydraulic dampers each consist of a first tube claim 5 , a second tube claim 5 , and a third tube in series claim 5 , the second tube in each of the hydraulic dampers having an ...

ASYMMETRIC CATALYSTS

The present invention relates to asymmetric catalysts, including redox-reconfigurable asymmetric catalysts. Methods of producing compounds having one or more stereocenters using the asymmetric catalysts of the present invention are also disclosed. 4. The catalyst according to claim 1 , wherein Ris a lower alkyl.5. The catalyst according to claim 1 , wherein Ris hydrogen.6. The catalyst according to claim 1 , wherein each catalytic moiety is selected from the group consisting of (thio)ureas; guanidines claim 1 , amides claim 1 , phenols claim 1 , carboxylic acids claim 1 , and other hydrogen bond donating groups; and a moiety of formula -E-NH—C(=G)-NH-E claim 1 , wherein Eand Eare each independently absent claim 1 , an alkyl claim 1 , an aryl claim 1 , or a heteroaryl and G is O claim 1 , S claim 1 , NR claim 1 , or —NR claim 1 , wherein each R is independently hydrogen claim 1 , an alkyl claim 1 , an alkenyl claim 1 , an alkynyl claim 1 , an aminyl claim 1 , a carbonyl claim 1 , a cycloalkyl claim 1 , a heterocyclyl claim 1 , an aryl claim 1 , a heteroaryl claim 1 , an arylalkyl claim 1 , or an acyl.7. The catalyst according to claim 6 , wherein each catalytic moiety is a moiety of formula -E-NH—C(=G)-NH-E.8. The catalyst according to claim 1 , wherein B or D is sulfur or selenium.9. The catalyst according to claim 1 , wherein B or D is oxygen.10. The catalyst according to claim 1 , wherein one of B and D is sulfur or selenium and the other of B and D is oxygen.11. The catalyst according to claim 1 , wherein M is Cu(I) claim 1 , Cu(II) claim 1 , Ag(I) claim 1 , Hg(II) claim 1 , Ni(II) claim 1 , Cd(II) claim 1 , Zn(II) claim 1 , Fe(II) claim 1 , Fe(III) claim 1 , Co(II) claim 1 , or another first row transition metal of oxidation state II or higher.12. The catalyst according to claim 1 , wherein the bond between M and B present and the bond between M and D is absent.13. The catalyst according to claim 1 , wherein the bond between M and B is absent and the bond ...

GEM-DINITRO ESTER ENERGETIC MATERIAL USING ESTERIFICATION AND PREPARATION METHOD THEREOF

This invention relates to a gem-dinitro ester energetic material represented by Chemical Formula 1 below, which is synthesized using esterification, and to a preparation method thereof: 2. The gem-dinitro ester energetic material of claim 1 , wherein the C5˜C15 substituted or unsubstituted linear or branched alkyl group is a substituted or unsubstituted linear or branched hexyl group claim 1 , a 2-ethylhexyl group claim 1 , an octyl group claim 1 , a 2-butyloctyl group or a 2-hexyldecyl group.4. The method of claim 3 , wherein the C5˜C15 substituted or unsubstituted linear or branched alkyl group is a substituted or unsubstituted linear or branched hexyl group claim 3 , a 2-ethylhexyl group claim 3 , an octyl group claim 3 , a 2-butyloctyl group or a 2-hexyldecyl group.5. The method of claim 3 , wherein esterifying the compound represented by Chemical Formula 2 with the compound represented by Chemical Formula 3 is performed in the presence of polyphosphoric acid.6. The method of claim 3 , wherein esterifying the compound represented by Chemical Formula 2 with the compound represented by Chemical Formula 3 is performed using dichloromethane or dichloroethane as a halogen solvent. This application claims the benefit of Korean Patent Application No. KR 10-2013-0130059, filed Oct. 30, 2013, which is hereby incorporated by reference in its entirety into this application.1. Technical FieldThe present invention relates to a gem-dinitro ester energetic material, which is synthesized using esterification, and to a preparation method thereof.2. Description of the Related ArtA plastic bonded explosive (PBX) has been developed to improve both performance and insensitivity of explosives, and typically includes a molecular explosive in crystalline form, such as RDX (Research Department Explosive), which typically exhibits explosive performance, and a binder system. The binder system is used in an amount of about 2˜20 wt % based on the total weight of PBX, and functions to impart ...

METHOD FOR PRODUCING NITRO COMPOUND

A compound represented by formula (1): 3. The method according to claim 2 , wherein claim 2 , in the step of reacting a compound represented by formula (2) with a compound represented by formula (3) and a secondary amine represented by formula (3′) to obtain a compound represented by formula (4′) claim 2 , the reaction is carried out in the presence of copper iodide.4. The method according to claim 2 , wherein the secondary amine is pyrrolidine.5. The method according to claim 1 , wherein claim 1 , in the step of oxidizing the compound represented by formula (4) with an oxidizing agent claim 1 , the oxidizing agent is a peroxide claim 1 , a permanganate or nitric acid.6. The method according to claim 2 , wherein claim 2 , in the step of oxidizing the compound represented by formula (4′) with an oxidizing agent claim 2 , the oxidizing agent is a peroxide claim 2 , a permanganate or nitric acid.7. The method according to claim 5 , wherein claim 5 , in the step of reducing a product by the oxidation reaction of the compound represented by formula (4) to obtain a compound represented by formula (8) claim 5 , the product is reduced by a borohydride compound.8. The method according to claim 6 , wherein claim 6 , in the step of reducing a product by the oxidation reaction of the compound represented by formula (4′) to obtain a compound represented by formula (8) claim 6 , the product is reduced by a borohydride compound.9. The method according to claim 1 , wherein claim 1 , in the step of halogenating the compound represented by formula (8) to obtain the compound represented by formula (1) claim 1 , the compound represented by formula (8) is halogenated with a phosphorus halide or a phosphorus oxyhalide.10. The method according to claim 2 , wherein claim 2 , in the step of halogenating the compound represented by formula (8) to obtain the compound represented by formula (1) claim 2 , the compound represented by formula (8) is halogenated with a phosphorus halide or a ...

METHOD FOR THE SYNTHESIS OF SOLID HETEROGENEOUS CHIRAL CATALYSTS AND THEIR USE IN STEREOSELECTIVE REACTIONS

This invention describes the methodology to produce solid heterogeneous chiral organocatalysts that can be used in condensation reactions. The catalysts can be recovered in a simple manner by filtration and can also be reused. 122-. (canceled)24. The compound of formula (I) according to claim 23 , wherein n is 0 and the α-amino acid is proline.25. The compound of formula (I) according to claim 23 , wherein n is 9 and the α-amino acid is proline.26. The compound of formula (I) according to claim 24 , wherein X is 1 and Y is 3.27. The compound of formula (I) according to claim 25 , wherein X is 1 and Y is 6.29. The method according to claim 28 , wherein step (i) comprises adding 0.5 to 3.0 equivalents of di-tert-butyl carbonate to a 0.1 M to 0.2 M solution of the α-amino acid in aqueous 1 claim 28 ,4-dioxane at a temperature from 0° C. to 30° C. claim 28 , wherein the aqueous 1 claim 28 ,4-dioxane has a ratio by volume of water: 1 claim 28 ,4-dioxane of 1:0.5 to 1:2.30. The method according to claim 29 , further comprising adding 0.3 to 3.0 equivalents of triethylamine to the reaction mixture of step (i) and reacting at a temperature of 20° C. to 40° C. for 12 to 72 hours.31. The method according to claim 28 , wherein step (ii) comprises:adding 0.5 to 3.0 equivalents of potassium carbonate and 0.5 to 3.0 equivalents of 0-(benzotriazole-1-il)-N,N,N′,N′-tetramethyluronium-tetrafluoroborate to a 0.1 M to 2.0 M solution of the protected α-amino acid in a solvent selected from the group consisting of acetonitrile and methanol under nitrogen at temperature of 0° C. to 40° C. for a period of 10 to 60 minutes to obtain a reaction mixture; andadding 0.5 to 5.0 equivalents of APTES to the reaction mixture, and reacting for a period of 12 to 72 hours at a temperature of 20° C. to 40° C. to obtain the protected and silanized α-amino acid.32. The method according to claim 31 , wherein the protected and silanized α-amino acid is purified and washed with acetonitrile or methanol.33. ...

GAMMA AMINO ACID BUILDING BLOCKS

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). 4. The compound of wherein Ris H or alkyl claim 3 , A-Aare each carbon claim 3 , Ris H or alkyl claim 3 , P is H claim 3 , methyl or acetyl claim 3 , and Y is nitro or protected amino.5. A method for preparing a compound of wherein Ris H comprising:contacting a cyclic compound of 5 or 6 ring atoms that includes a nitroethylene moiety within the ring and that optionally includes one or two nitrogen atoms in the ring, wherein the carbon atoms in the ring are optionally substituted and the optional nitrogen atom or atoms in the ring are optionally substituted by a nitrogen protecting group; andan aldehyde that has at least one α-hydrogen;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'in the presence of an organic solvent, and a proline derivative, for a period of time sufficient to provide the compound of .'}6. The method of wherein the aldehyde has an α-methylene group or an α-methine group.7. The method of wherein the contacting is carried out in the presence of a carboxylic acid claim 5 , the proline derivative is a chiral pyrrolidine catalyst claim 5 , and the compound of is prepared in at least about 80% enantiomeric purity.8. The method of further comprising reducing an aldehyde moiety of the compound of to an alcohol claim 5 , oxidizing the resulting alcohol to a carboxylic acid claim 5 , reducing the nitro moiety of the compound of to an amine claim 5 , or a combination thereof.12. The method of wherein the contacting is carried out in the presence of a carboxylic acid claim 11 , the proline derivative is a chiral ...

Process for Manufacturing Pibrentasvir Active Drug Substance

The present invention relates to compositions of pibrentasvir, drug products thereof, and processes and intermediates for the preparation thereof. This invention relates to the drug product, active drug substance, intermediates, and processes of pibrentasvir, a NS5A inhibitor that is useful in the treatment of hepatitis C. 2. The compound of claim 1 , wherein the compound of formula (IIa) is in solid form.3. The compound of claim 1 , wherein the compound of formula (IIa) is in crystalline form.5. The compound of claim 3 , having an X-ray powder diffraction pattern comprising peaks at ±0.2 of 11.2 claim 3 , 11.9 claim 3 , 14.7 claim 3 , 16.3 claim 3 , 17.7 claim 3 , 19.4 claim 3 , 19.9 claim 3 , 22.7 claim 3 , 25.0 claim 3 , 27.0° 2θ claim 3 , when measured at about 25° C. with Cu-Kai radiation at 1.5406 {acute over (Å)}.8. The process of claim 7 , further comprising precipitating Compound (IIa).9. The process of claim 8 , further comprising separating solid Compound (IIa) from a filtrate comprising Compound (I).14. The process of claim 13 , further comprising precipitating Compound (IIa).15. The process of claim 14 , further comprising separating solid Compound (IIa) from a filtrate comprising Compound (I).16. The process of claim 15 , further comprising claim 15 ,oxidizing Compound (IIa) to form Compound (III).17. The process of claim 16 , further comprising claim 16 ,converting Compound (I) to pibrentasvir.21. The composition of claim 20 , wherein the process further comprises claim 20 , converting Compound (III) to pibrentasvir.25. The drug product of claim 24 , wherein the drug substance comprises not more than 0.80 weight percent of the impurity Compound (xi).29. The drug product of claim 28 , wherein the process further comprises claim 28 ,converting Compound (III) to pibrentasvir. This invention relates to the drug product, active drug substance, intermediates, and processes of pibrentasvir, a NS5A inhibitor that is useful in the treatment of hepatitis C.The ...

METHOD FOR PRODUCING NITRO COMPOUND

A compound represented by formula (1): 3. The method according to claim 2 , wherein claim 2 , in the step of reacting a compound represented by formula (2) with a compound represented by formula (3) and a secondary amine represented by formula (3′) to obtain a compound represented by formula (4′) claim 2 , the reaction is carried out in the presence of copper iodide.4. The method according to claim 2 , wherein the secondary amine is pyrrolidine.5. The method according to claim 1 , wherein claim 1 , in the step of reacting the compound represented by formula (4) with a hypohalogenous acid or a salt thereof to obtain a compound represented by formula (5) claim 1 , the hypohalogenous acid or salt thereof is hypochlorous acid or a salt thereof.6. The method according to claim 2 , wherein claim 2 , in the step of reacting the compound represented by formula (4′) with a hypohalogenous acid or a salt thereof to obtain a compound represented by formula (5) claim 2 , the hypohalogenous acid or salt thereof is hypochlorous acid or a salt thereof.7. The method according to claim 1 , wherein claim 1 , in the step of reducing the compound represented by formula (5) to obtain the compound represented by formula (1) claim 1 , the compound represented by formula (5) is reduced in the presence of a heterogeneous platinum group catalyst and formic acid or a salt thereof.8. The method according to claim 2 , wherein claim 2 , in the step of reducing the compound represented by formula (5) to obtain the compound represented by formula (1) claim 2 , the compound represented by formula (5) is reduced in the presence of a heterogeneous platinum group catalyst and formic acid or a salt thereof.9. The method according to claim 1 , wherein Ris a methyl group claim 1 , and Rand Rare a hydrogen atom.10. The method according to claim 2 , wherein Ris a methyl group claim 2 , and Rand Rare a hydrogen atom. The present invention relates to a method for producing a nitro compound.WO2013/162072 ...

METHOD FOR THE SYNTHESIS OF SOLID HETEROGENEOUS CHIRAL CATALYSTS AND THEIR USE IN STEREOSELECTIVE REACTIONS

This invention describes the methodology to produce solid heterogeneous chiral organocatalysts that can be used in condensation reactions. The catalysts can be recovered in a simple manner by filtration and can also be reused. 2. The compound of formula (I) according to claim 1 , wherein n is 0 and the α-amino acid is proline.3. The compound of formula (I) according to claim 1 , wherein n is 9 and the α-amino acid is proline.4. The compound of formula (I) according to claim 2 , wherein X is 1 and Y is 3.5. The compound of formula (I) according to claim 3 , wherein X is 1 and Y is 6.6. A method for forming chiral carbon-carbon bonds comprising performing a reaction for forming carbon-carbon bonds in the presence of the compound of formula (I) according to as catalyst claim 1 , wherein the reaction for forming carbon-carbon bonds is selected from the group consisting of an aldol condensation claim 1 , a Michael addition claim 1 , a Mannich reaction claim 1 , and a Henry reaction.7. The method according to claim 6 , wherein the reaction for forming carbon-carbon bonds is performed in an aqueous reaction medium or an organic reaction medium at a temperature of −78° C. to 40° C.8. The method according to claim 6 , wherein the reaction for forming carbon-carbon bonds is performed in an aqueous reaction medium comprising a phosphate buffer having pH 7 at a temperature between 0° C. and 10° C. This application is a Divisional of co-pending U.S. patent application Ser. No. 14/085,003 filed Nov. 20, 2013, and the disclosure of which is incorporated herein by reference.This invention describes a method for the synthesis of solid heterogeneous chiral catalysts and their use in stereoselective reactions. Particularly, the invention describes a methodology for obtaining organic catalysts immobilized in a silicon oxide matrix. These catalysts are applied in some stereoselective reactions; they are easily recovered from the reaction mixture and are reused.There is a set of ...

Crystalline Inhibitor of 4-Hydroxyphenylpyruvate Dioxygenase

The present invention relates to an improved synthesis and crystallization process of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, also known as nitisinone or NTBC. 111-. (canceled)12. A method of inhibiting 4-hydroxyphenylpyruvate dioxygenase enzyme in a patient , the method comprising administering to a patient in need thereof a therapeutically effective amount of crystalline 2-(2-nitro-4-trifluoromethylbenzoyl)-1 ,3-cyclohexanedione having a X-ray powder diffraction pattern with at least five specific peaks at about 2-theta=7.4 , 14.7 , 15.7 , 22.9 , and 29.7 , wherein said peaks may be plus or minus 0.2° 2-theta and have an intensity of at least 30%.13. The method of claim 12 , wherein the patient is suffering from a disease selected from the group consisting of oculocutaneous/ocular albinism claim 12 , microbial infections claim 12 , restless leg syndrome claim 12 , alkaptonuria claim 12 , and hereditary tyrosinemia type 1.14. The method of claim 13 , wherein the disease to be treated is hereditary tyrosinemia type 1.15. The method of claim 12 , wherein the therapeutically effective amount of the crystalline 2-(2-nitro-4-trifluoromethylbenzoyl)-1 claim 12 ,3-cyclohexanedione is from about 0.1 to about 2 mg/kg/day.16. The method of claim 15 , wherein the therapeutically effective amount of crystalline 2-(2-nitro-4-trifluoromethylbenzoyl)-1 claim 15 ,3-cyclohexanedione is from about 1 to about 2 mg/kg/day.17. A method of treating oculocutaneous/ocular albinism claim 15 , microbial infections claim 15 , restless leg syndrome claim 15 , alkaptonuria claim 15 , or hereditary tyrosinemia type 1 claim 15 , the method comprising administering to a patient in need thereof a therapeutically effective amount of crystalline 2-(2-nitro-4-trifluoromethylbenzoyl)-1 claim 15 ,3-cyclohexanedione having X-ray powder diffraction pattern with at least five specific peaks at about 2-theta=7.4 claim 15 , 14.7 ...

METHOD OF SYNTHESIZING (1R,2R)-NITROALCOHOL COMPOUND

Disclosed is a method of synthesizing a (1R,2R)-nitroalcohol compound of formula (I), as shown in the following reaction scheme, including: subjecting a compound of formula (II) and a compound of formula (III) to a condensation reaction in an organic solvent in the presence of a copper complex generated in situ from a chiral (1S,2R)-amino alcohol ligand and a cupric salt to produce the (1R,2R)-nitroalcohol compound of formula (I), where Rand Rare defined in the same manner as that in the specification. The method involves mild reaction conditions, excellent diastereoselectivity and high chemical yield, and thus it is suitable for industrial applications. 3. The method of claim 2 , wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S claim 2 ,2R)-amino alcohol ligand is 1:1.1-8:0.05-0.15:0.08-0.2.4. The method of claim 3 , wherein a molar ratio of the compound of formula (II) to the compound of formula (III) to the cupric salt to the chiral (1S claim 3 ,2R)-amino alcohol ligand is 1: 2-6:0.05-0.15:0.08-0.2.5. The method of claim 1 , wherein the chiral (1S claim 1 ,2R)-amino alcohol ligand is (1S claim 1 ,2R)-1 claim 1 ,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol claim 1 , (1S claim 1 ,2R)-2-(dimethylamino)-1 claim 1 ,2-diphenylethan-1-ol or (1S claim 1 ,2R)-2-(diisopropylamino)-1 claim 1 ,2-diphenylethan-1-ol.6. The method of claim 2 , wherein the chiral (1S claim 2 ,2R)-amino alcohol ligand is (1S claim 2 ,2R)-1 claim 2 ,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol claim 2 , (1S claim 2 ,2R)-2-(dimethylamino)-1 claim 2 ,2-diphenylethan-1-ol or (1S claim 2 ,2R)-2-(diisopropylamino)-1 claim 2 ,2-diphenylethan-1-ol.7. The method of claim 3 , wherein the chiral (1S claim 3 ,2R)-amino alcohol ligand is (1S claim 3 ,2R)-1 claim 3 ,2-diphenyl-2-(pyrrolidin-1-yl)ethan-1-ol claim 3 , (1S claim 3 ,2R)-2-(dimethylamino)-1 claim 3 ,2-diphenylethan-1-ol or (1S claim 3 ,2R)-2-(diisopropylamino)-1 claim 3 ,2- ...

PREPARATION OF FINGOLIMOD AND ITS SALTS

The present application provide processes for the preparation of fingolimod and its pharmaceutically acceptable salts, process for the purification of fingolimod hydrochloride and process for the preparation of amorphous fingolimod hydrochloride. 2. The process of claim 1 , wherein the salt of formula (Ia) is a hydrochloride salt.3. The process of claim 1 , wherein the Lewis acid used in step a) is selected from TiCl claim 1 , AlCl claim 1 , or BF.4. The process of claim 1 , wherein the trialkylsilanes used in step a) are selected from triethylsilane claim 1 , trimethylsilane claim 1 , or triisopropyl silane.5. The process of claim 1 , wherein step a) is carried out in the presence of a halogenated hydrocarbon solvent claim 1 , a hydrocarbon solvent or from mixtures thereof.6. The process of claim 1 , wherein step b) is carried out in the presence of a base selected from an organic base such as diethylamine claim 1 , triethylamine claim 1 , n-butylamine claim 1 , propylamine claim 1 , diisopropylethylamine claim 1 , dicyclohexylamine or an inorganic base such as sodium carbonate claim 1 , potassium carbonate.7. The process of claim 1 , wherein step b) is carried out in the presence of an alcohol such as methanol claim 1 , ethanol claim 1 , polar aprotic solvents such as dimethylformamide claim 1 , dimethyl sulfoxide claim 1 , tetrahydrofuran claim 1 , acetone claim 1 , acetonitrile claim 1 , and aromatic solvents such as toluene claim 1 , xylene or mixtures thereof.8. The process of claim 1 , wherein the reducing agent used in step a) is selected from sodium borohydride claim 1 , lithium borohydride claim 1 , lithium aluminium hydride claim 1 , Pd on carbon claim 1 , Raney® nickel claim 1 , or Pd(OH) claim 1 , under a hydrogen atmosphere.9. The process of claim 1 , wherein step c) is carried out in the presence of an alcohol selected from methanol claim 1 , ethanol claim 1 , a polar aprotic solvent selected from dimethylformamide claim 1 , dimethyl sulfoxide claim 1 ...

FLUORINE-CONTAINING COMPOUND, SUBSTRATE FOR PATTERN FORMATION, PHOTODEGRADABLE COUPLING AGENT, PATTERN FORMATION METHOD, AND COMPOUND

A fluorine-containing compound represented by a following general formula (1) is provided. [In the general formula (1), X represents a halogen atom or an alkoxy group, Rrepresents a branched chain or cyclic alkyl group having 3 to 10 carbon atoms, and Rand Rrepresent fluorinated alkoxy groups. n represents an integer of 0 or greater. ] 2. The fluorine-containing compound according to claim 1 , wherein Rrepresents an isopropyl group claim 1 , an isobutyl group claim 1 , or a tert-butyl group.3. The fluorine-containing compound according to claim 1 , wherein Ror Rrepresent fluorinated alkoxy groups having 5 or more carbon atoms.4. A substrate for pattern formation having a surface chemically modified with the fluorine-containing compound according to .5. A photodegradable coupling agent formed of the fluorine-containing compound according to .6. A pattern formation method for forming a pattern on a work surface of an object claim 1 , the pattern formation method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'chemically modifying the work surface using the fluorine-containing compound according to ;'}generating a latent image formed of a hydrophilic region and a water repellent region by irradiating the chemically modified work surface with light having a predetermined pattern; anddisposing a pattern formation material in the hydrophilic region or the water repellent region.7. A pattern formation method for forming a circuit pattern for an electronic device on a substrate having flexibility claim 1 , the pattern formation method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'chemically modifying an entire surface or a specific region of the substrate using the fluorine-containing compound according to ;'}generating a latent image of the circuit pattern due to a difference in hydrophilicity and water repellency on the chemically modified surface of the substrate by irradiating with light energy having a distribution corresponding to the ...

Small Molecules That Covalently Modify Transthyretin

A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and 2. The compound according to aspect 1 , wherein X is a carboxylic ester or thioester , an azetidin-2-one , a Michael acceptor , an epoxide , aziridine or thienyl group or a β-haloacetyl group.3. The compound according to aspect 2 , wherein n is one.4. The compound according to aspect 3 , wherein circle A is an aromatic or heteroaromatic ring structure containing one 5- or 6-membered ring.5. The compound according to aspect 4 , wherein said heterocyclic ring contains one to three heteroatoms that are oxygen , nitrogen , sulfur and mixtures thereof.6. The compound according to aspect 5 , wherein said heterocyclic ring contains 6-members and the heteroatom is nitrogen.7. The compound according to aspect 3 , wherein circle A is an aromatic or heteroaromatic ring structure containing two fused rings having one 5- and one 6-membered ring or two 6-membered rings.8. The compound according to aspect 7 , wherein said heterocyclic ring contains one to three heteroatoms that are oxygen , nitrogen , sulfur and mixtures thereof.9. The compound according to aspect 1 , wherein L is Q=Q.10. The compound according to aspect 1 , wherein Z is L.12. The compound according to aspect 11 , wherein structure A is a six-membered ring.13. The compound according to aspect 12 , wherein the six-membered ring is a hydrocarbyl ring.14. The compound according to aspect 12 , wherein Z is NRR.16. The compound according to aspect 15 , wherein Lis a metal ion chelating group.17. The compound according to aspect 16 , wherein said metal ion chelating group chelates a radionuclide.18. The compound according to aspect 16 , wherein said metal ion chelating group chelates a ...

PROCESS FOR THE PREPARATION OF 1-(3,5-DICHLOROPHENYL)-2,2,2-TRIFLUOROETHANONE AND DERIVATIVES THEREOF

A process for the preparation of a compound of formula (I) wherein Ris hydrogen, fluoro or chloro; which process comprises: a) reacting a compound of formula (II) wherein Ris hydrogen, fluoro or chloro; with a nitration agent to the compound of formula (III) wherein Ris hydrogen, fluoro or chloro; b) reacting the compound of formula (III) with trichloroisocyanuric acid in the presence of sulfuric acid or fuming sulfuric acid to the compound of formula (IV) wherein R1 is hydrogen, fluoro or chloro; and c) reacting the compound of formula (III) with chlorine gas at a temperature from 180° C. to 250° C. to the compound of formula (I). 2. The process according to claim 1 , characterized in that the nitration agent is selected from sulfuric acid claim 1 , nitric acid and their salts.3. The process according to claim 1 , characterized in that the process is performed without isolating the intermediate of formula III.5. (canceled) The present invention relates to the preparation of halo-substituted 1-aryl-2,2,2-trifluoro-ethanones (compounds Ia, Ib and Ic):and to intermediates useful for said process. Said compounds are important intermediates for the preparation of pesticidally active isoxazoline-substituted benzamides as for example 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone (Ic) disclosed in EP 1932836A1.Typically said compounds of formula Ia, Ib and Ic are prepared by reaction of the corresponding organometallic reagents derived from halo-substituted 5-bromo-benzenes of formula VIa, VIb and VIcwith the derivatives of trifluoroacetic acid (for example ethyl trifluoroacetate). For example the preparation of 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)ethanone (I b) is described in WO 2012/120135.The corresponding bromo derivatives of the formula VIa, VIb and VIc are not easily available and prepared via multistep procedures. For example, 5-bromo-1,2,3-trichloro-benzene (VI b) can be prepared as described in Sott, R.; Hawner, C.; Johansen, J. E. Tetrahedron ...

PHOTO-CLEAVABLE PRIMER COMPOSITIONS AND METHODS OF USE

In one embodiment, the present application discloses a photo-cleavable surface binding compound of the Formula I and Formula II: 3. The surface binding compound of claim 1 , wherein each EG and EG1 is independently selected from the group consisting of a Calkyl claim 1 , CH═CHC(O)O— claim 1 , CH═C(Calkyl)C(O)O— claim 1 , CH═C(phenyl)C(O)O— claim 1 , CH═C(Calkyl)S(O)O— claim 1 , isocyanate claim 1 , epoxy claim 1 , oxetanyl claim 1 , styrenyl claim 1 , vinyl ether claim 1 , —Ar-(BG) claim 1 , phenyl and naphthyl.4. The surface binding compound of claim 1 , wherein each EG and EG2 is independently selected from the group consisting of imidazolyl claim 1 , indolyl claim 1 , —NRRR claim 1 , —PO claim 1 , —NRRRX claim 1 , —POY claim 1 , —SOY claim 1 , wherein each R claim 1 , Rand Ris independently H and Calkyl claim 1 , Xis Cl claim 1 , Br and Iand Y is H or —NRRR.5. The surface binding compound of claim 1 , wherein each of SP1 claim 1 , SP2 and SP3 is a spacer independently selected from the group consisting of —(CH)— claim 1 , —NH(CH)NH— claim 1 , —NHCHCHC(O)— claim 1 , —C(O)NHCHCHNH— claim 1 , —NHCHC(O)— claim 1 , —NHC(O)— claim 1 , —C(O)N— claim 1 , —NC(O)— claim 1 , —C(O)NH— claim 1 , —NCHC(O)— claim 1 , —C(O)NCH— claim 1 , —(CHCHO)— claim 1 , —(CHCHO)CHCH— claim 1 , —CHCH—(CHCHO)— and —OCH(CHO—)-.6. The surface binding compound of claim 1 , wherein each of SP1 claim 1 , SP2 and SP3 is a spacer independently selected from the group consisting of —NRR— claim 1 , —PO— claim 1 , —NRRX— claim 1 , —POY— claim 1 , —SOY— claim 1 , —(CH)—NRR— claim 1 , —(CH)—PO— claim 1 , —(CH)—NRR—X— claim 1 , —(CH)—POY— and —O—PO(O)O—(CH)—N(RR)—.7. The surface binding compound of claim 1 , wherein each SP1 claim 1 , SP2 and SP3 is a spacer independently selected from the group consisting of —CHCH—C(O)NHCHCHNH—C(O)NCH— claim 1 , —NHC(O)—(CHCHC)—(CH)— claim 1 , —(CHCHO)CHCH—C(O)NCH—(CHCHO)CHCH— claim 1 , —NHCHCHC(O)—(CH)—PO— claim 1 , —PO—(CH)—NRRX— claim 1 , —(CHCHO)—(CH)—PO claim 1 , — ...

SURFACE PRIMER COMPOSITIONS AND METHODS OF USE

In one embodiment, the present application discloses a surface binding compound of the Formula I or Formula II: 3. The surface binding compound of claim 1 , wherein each EG is independently selected from the group consisting of a Calkyl claim 1 , optionally substituted Calkyl claim 1 , —N(CH)CHOH claim 1 , —N(CHOH)CH claim 1 , —N(CHOH) claim 1 , —N(CHCH)CHCHOH claim 1 , —N(CHCHOH)CHCH claim 1 , —N(CHCHOH) claim 1 , —N(CH)CHSH claim 1 , —N(CHSH)CH claim 1 , —N(CHSH) claim 1 , —N(CHCH)CHCHSH claim 1 , —N(CHCHSH)CHCH claim 1 , —N(CHCHSH) claim 1 , —N(CH)CHNH claim 1 , —N(CHNH)CH claim 1 , —N(CHNH) claim 1 , —N(CHCH)CHCHNH claim 1 , —N(CHCHNH)CHCH claim 1 , —N(CHCHNH) claim 1 , —N(CH)CHOHX claim 1 , —N(CHOH)CHX claim 1 , —N(CHOH)X claim 1 , —N(CHCH)CHCHOHX claim 1 , —N(CHCHOH)CHCHX claim 1 , —N(CHCHOH)X claim 1 , —N(CH)CHSHX claim 1 , —N(CHSH)CHX claim 1 , —N(CHSH)X claim 1 , —N(CHCH)CHCHSHX claim 1 , —N(CHCHSH)CHCHX claim 1 , —N(CHCHSH)X claim 1 , —N(CH)CHNHX claim 1 , —N(CHNH)CH claim 1 , X claim 1 , —N(CHNH)X claim 1 , —N(CHCH)CHCHNHX claim 1 , —N(CHCHNH)CHCHX claim 1 , —N(CHCHNH)X claim 1 , CH═CHC(O)O— claim 1 , CH═C(Calkyl)C(O)O— claim 1 , CH═C(phenyl)C(O)O— claim 1 , CH═CHS(O)O— claim 1 , isocyanate claim 1 , epoxy claim 1 , oxetanyl claim 1 , styrenyl claim 1 , vinyl ether claim 1 , —Ar—(BG) claim 1 , phenyl and naphthyl claim 1 , where X is Cl claim 1 , Br and I.4. The surface binding compound of claim 1 , wherein each EG is independently selected from the group consisting of imidazolyl claim 1 , imidazolinium claim 1 , indolinium claim 1 , indolyl claim 1 , —NRRR claim 1 , —PO claim 1 , —NRRRX claim 1 , —POY claim 1 , —SOY claim 1 , wherein each R claim 1 , Rand Ris independently H and Calkyl and Calkyl substituted with 1 claim 1 , 2 or 3 —OH claim 1 , 1 claim 1 , 2 or 3 —SH or 1 claim 1 , 2 or 3 —NH claim 1 , X is Cl claim 1 , Br and I and Y is H or —NRRR.5. The surface binding compound of claim 1 , wherein each of SP1 claim 1 , SP2 and SP3 is a spacer ...

METHOD OF PREPARING CHIRAL KETONES FROM ALDEHYDES

Present invention relates to a method of preparing a chiral α- or β-substituted ketone from the corresponding β- or γ-substituted aldehyde, wherein the ketone has formula (I), (III) or (V), and the corresponding aldehyde has formula (II), (IV) or (VI), respectively, the method comprising reacting the aldehyde of formula (II), (IV) or (VI) in the presence of an amine, oxygen and an organic solvent, wherein the reaction is carried out in the absence of a metal-based catalyst or a metal-based oxidant, wherein: R is H, a substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Calkenyl, substituted or unsubstituted C-Calkynyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted C-Ccycloalkenyl, substituted or unsubstituted C-Cheterocycloalkyl, substituted or unsubstituted C-Cheterocycloalkenyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted C-Cheteroaryl; and R′ is H, a substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Calkenyl, substituted or unsubstituted C-Calkynyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted C-Ccycloalkenyl, substituted or unsubstituted C-Cheterocycloalkyl, substituted or unsubstituted C-Cheterocycloalkenyl, substituted or unsubstituted C-Caryl, or substituted or unsubstituted C-Cheteroaryl. 2. The method of claim 1 , wherein the amine is a compound of formula (VII) claim 1 ,{'br': None, 'sub': 1', '2, 'R—NHR\u2003\u2003(VII),'}wherein:{'sub': '1', 'Ris a substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alicyclic, substituted or unsubstituted heteroalicyclic, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocycloalkyl; and'}{'sub': 2', '1, 'Ris H or combines with Rto form with the nitrogen to which they are attached a cyclic group selected from substituted or unsubstituted heterocycloalkyl and substituted or ...

Aldehyde-selective wacker-type oxidation of unbiased alkenes

This disclosure is directed to methods of preparing organic aldehydes, each method comprising contacting a terminal olefin with an oxidizing mixture comprising: (a) a dichloro-palladium complex; (b) a copper complex; (c) a source of nitrite; under aerobic reaction conditions sufficient to convert at least a portion of the terminal olefin to an aldehyde.

NOVEL PROCESS FOR PREPARING PHENYLCYCLOPROPYLAMINE DERIVATIVES USING NOVEL INTERMEDIATES

Provided herein is a novel process for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein is a novel, commercially viable and industrially advantageous process for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. The intermediate is useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity. 2. The process of claim 1 , wherein the halogen atom in the compounds of formulae II claim 1 , III claim 1 , IV claim 1 , V claim 1 , VI and VII is F; and wherein the leaving group ‘X’ in the compound of formula VIII is Cl.3. The process of claim 1 , wherein the R claim 1 , Rand Rin the compounds of formulae II claim 1 , III claim 1 , IV claim 1 , V claim 1 , VI and VII are H claim 1 , and wherein the Rand Rare F.4. The process of claim 1 , wherein the first solvent used in step-(a) is selected from the group consisting of an aliphatic or alicyclic hydrocarbon claim 1 , a chlorinated aliphatic or aromatic hydrocarbon claim 1 , an aromatic mono or dinitro hydrocarbon claim 1 , and mixtures thereof; wherein the second solvent used in step-(b) is selected from the group consisting of a ketone claim 1 , an aliphatic amide claim 1 , a nitrile claim 1 , a hydrocarbon claim 1 , a cyclic ether claim 1 , an aliphatic ether claim 1 , a polar aprotic solvent claim 1 , and mixtures thereof; wherein the third solvent used in step-(c) is selected from the group consisting of a hydrocarbon claim 1 , a cyclic ether claim 1 , an aliphatic ether claim 1 , a chlorinated hydrocarbon claim 1 , and mixtures thereof; wherein the fourth solvent used in step-(d) is selected from the group consisting of a hydrocarbon claim 1 , cyclic ethers claim 1 , an ether claim 1 , an ester claim 1 , a nitrile claim 1 , an aliphatic amide claim 1 , a chlorinated hydrocarbon claim 1 ...

SMALL MOLECULE XANTHINE OXIDASE INHIBITORS AND METHODS OF USE

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled) This application is a divisional application and claims priority to U.S. patent application Ser. No. 13/790,083 filed on Mar. 8, 2013 entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use” which claims the benefit of and incorporates by reference U.S. provisional patent Application Ser. No. 61/734,409, filed on Dec. 7, 2012 and entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use.” Which are incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then catalyzes the oxidation of xanthine to uric acid. Meanwhile, reactive oxygen species (ROS), including superoxide and HO, are generated during this process. Uric acid can serve as an antioxidant to prevent macromolecular damage by ROS. However, overproduction of uric acid can cause hyperuricemia and lead to gout and other diseases. Therefore, maintaining uric acid at normal levels represents an important therapeutic goal for the prevention of gout and related disorders. For most patients with primary gout, overproduction of uric acid is the primary cause of ...

DERIVATIZATION OF CARBON

Derivatization of an elemental carbon surface is accomplished by exposing the carbon surface to an aprotic solvent containing a hydrazone molecule of formula (I) or the corresponding salt of formula (II) wherein Ris an organic group, and Ris an organic group or hydrogen and decomposing the hydrazone in the presence of elemental carbon to create a carbene moiety of formula (III): which attaches to the carbon surface. The attached groups may be redox active so that the derivatized carbon may be used in an electrochemical sensor. 2. A process according to wherein X is a group of the formula —SO—Y.3. A process according to wherein Y is an aromatic group bearing one or more alkyl substituents.4. A process according to wherein at least one of the Rand Rgroups comprises an aromatic group such that the carbon atom of the >C═N—N< hydrazone group can form delocalised bonds with the aromatic ring.5. A process according to wherein at least one of the Rand Rgroups comprises an aromatic group which is one of phenyl claim 4 , napthyl or anthracenyl or comprises an aromatic ring connected to a vinyl group.6. A process according to wherein at least one of the Rand Rgroups comprises an aromatic ring or system bearing at least one substituent which is a functional group able to undergo electrochemical redox reaction.7. A process according to wherein at least one of the Rand Rgroups comprises an aromatic quinone or is an aromatic group bearing a nitro substituent.8. A process according to wherein at least one of the Rand Rgroups comprises a ferrocenyl group.9. A process according to wherein the elemental carbon is graphite claim 1 , glassy carbon claim 1 , carbon fibres claim 1 , carbon black claim 1 , carbon paste claim 1 , boron doped diamond claim 1 , carbon epoxy claim 1 , carbon nanotubes or graphene.10. A process according to wherein the elemental carbon is in particulate form and the process further comprises immobilizing the derivatized elemental carbon on an electrode.11. A ...

METHOD OF PRODUCING OPTICALLY ACTIVE COMPOUND

An optically active compound production method using a column reactor, a column for column reactor is charged with asymmetric catalyst particles to produce the column reactor, and reaction compound is introduced into column reactor to bring reaction compound into contact with asymmetric catalyst particles, whereby reaction compound is converted to optically active compound. Asymmetric catalyst particles are preferably resin particles that are prepared from a monomer composition containing a proline derivative monomer having unsaturated bond and radical polymerization initiator and serve as catalyst for enamine mechanism reaction. Asymmetric catalyst particles are preferably resin particles prepared by micro-channel method including injecting monomer composition into continuous phase to thereby form droplets of monomer composition in continuous phase and then heating droplets to cause proline derivative monomer having an unsaturated bond to undergo radical polymerization. 1. An optically active compound production method using a column reactor prepared by charging a column for the column reactor with asymmetric catalyst particles , whereinthe asymmetric catalyst particles are resin particles prepared from a monomer composition containing a monomer having a chiral source, anda reaction compound is introduced into the column reactor to bring the reaction compound into contact with the asymmetric catalyst particles, whereby the reaction compound is converted to an optically active compound.2. The production method according to claim 1 , wherein the asymmetric catalyst particles are resin particles prepared from a monomer composition containing claim 1 , as the monomer having a chiral source claim 1 , a proline derivative monomer having an unsaturated bond and further containing a radical polymerization initiator claim 1 , the resin particles being capable of serving as a catalyst for an aldol reaction.3. The production method according to claim 1 , wherein the ...

METHODS OF INHIBITING XANTHINE OXIDASE ACTIVITY IN A CELL

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled)17. The method of claim 16 , further comprising administering a second therapeutic agent to the subject.18. The method of claim 17 , wherein the second therapeutic agent is an anti-gout agent.19. The method of claim 18 , wherein the anti-gout agent is selected from the group consisting of allopurinol claim 18 , benzbromarone claim 18 , colchicine claim 18 , probenecid claim 18 , and sulfinpyrazone.20. The method of claim 19 , wherein the second therapeutic agent is an anti-inflammatory agent.21. The method of claim 17 , wherein the second therapeutic agent is an antioxidant.22. The method of claim 16 , wherein the compound is administered orally.25. The method of wherein the method further comprises selecting a subject having gout or hyperuricemia. This application is a continuation application and claims priority to U.S. patent application Ser. No. 13/790,083 filed on Mar. 8, 2013 entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use” which claims the benefit of and incorporates by reference U.S. provisional patent Application Ser. No. 61/734,409, filed on Dec. 7, 2012 and entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use.” Which are incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form ...

Small Molecules That Covalently Modify Transthyretin

A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and 2. The compound according to aspect 1 , wherein X is a carboxylic ester or thioester , an azetidin-2-one , a Michael acceptor , an epoxide , aziridine or thienyl group or a β-haloacetyl group.3. The compound according to aspect 2 , wherein n is one.4. The compound according to aspect 3 , wherein circle A is an aromatic or heteroaromatic ring structure containing one 5- or 6-membered ring.5. The compound according to aspect 4 , wherein said heterocyclic ring contains one to three heteroatoms that are oxygen , nitrogen , sulfur and mixtures thereof.6. The compound according to aspect 5 , wherein said heterocyclic ring contains 6-members and the heteroatom is nitrogen.7. The compound according to aspect 3 , wherein circle A is an aromatic or heteroaromatic ring structure containing two fused rings having one 5- and one 6-membered ring or two 6-membered rings.8. The compound according to aspect 7 , wherein said heterocyclic ring contains one to three heteroatoms that are oxygen , nitrogen , sulfur and mixtures thereof.9. The compound according to aspect 1 , wherein L is Q=Q.10. The compound according to aspect 1 , wherein Z is L.12. The compound according to aspect 11 , wherein structure A is a six-membered ring.13. The compound according to aspect 12 , wherein the six-membered ring is a hydrocarbyl ring.14. The compound according to aspect 12 , wherein Z is NRR.16. The compound according to aspect 15 , wherein Lis a metal ion chelating group.17. The compound according to aspect 16 , wherein said metal ion chelating group chelates a radionuclide.18. The compound according to aspect 16 , wherein said metal ion chelating group chelates a ...

Small Molecule Xanthine Oxidase Inhibitors and Methods of Use

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled)17. The method according to claim 16 , wherein said compound is compound I or a pharmaceutically acceptable salt thereof.18. The method according to claim 16 , wherein said compound is compound II or a pharmaceutically acceptable salt thereof.20. The method according to claim 20 , wherein said compound is compound I or a pharmaceutically acceptable salt thereof.21. The method according to claim 20 , wherein said compound is compound II or a pharmaceutically acceptable salt thereof. This application is a divisional application and claims priority to U.S. patent application Ser. No. 13/790,083 filed on Mar. 8, 2013 entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use” which claims the benefit of and incorporates by reference U.S. provisional patent Application Ser. No. 61/734,409, filed on Dec. 7, 2012 and entitled “Small Molecule Xanthine Oxidase Inhibitors And Methods Of Use.” Which are incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then catalyzes the oxidation of xanthine to uric acid. Meanwhile, reactive oxygen ...

GAMMA AMINO ACID BUILDING BLOCKS

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). 19-. (canceled)12. The method of wherein the contacting is carried out in the presence of a carboxylic acid claim 11 , the proline derivative is a chiral pyrrolidine catalyst claim 11 , and the compound of Formula VI is prepared in an enantiomerically enriched form.1318-. (canceled)19. The compound of claim 10 , wherein Y is NOor NH.20. The compound of claim 10 , wherein R is H or OH.21. The compound of claim 10 , wherein Y is NOor NHand R is H or OH.22. The compound of claim 10 , wherein Ris alkyl claim 10 , cycloalkyl claim 10 , aryl claim 10 , heteroaryl claim 10 , or heterocycle; wherein the alkyl claim 10 , cycloalkyl claim 10 , aryl claim 10 , heteroaryl claim 10 , or heterocycle of Ris optionally substituted with one to five alkyl claim 10 , alkoxy claim 10 , fluoro claim 10 , protected hydroxy claim 10 , aryl claim 10 , (aryl)alkyl claim 10 , heteroaryl claim 10 , heterocycle claim 10 , cycloalkyl claim 10 , alkanoyl claim 10 , alkoxycarbonyl claim 10 , protected amino claim 10 , alkylamino claim 10 , dialkylamino claim 10 , acylamino claim 10 , trifluoromethyl claim 10 , trifluoromethoxy claim 10 , carboxy claim 10 , carboxyalkyl claim 10 , keto claim 10 , arylsulfonyl claim 10 , cyano claim 10 , or azide groups.23. The compound of claim 22 , wherein Y is NOor NH.24. The compound of claim 22 , wherein R is H or OH.25. The compound of claim 22 , wherein Y is NOor NHand R is H or OH. This application is a divisional of U.S. patent application Ser. No. 14/166,007, filed Jan. 28, 2014, which is a divisional of U.S. patent ...

Small Molecule Xanthine Oxidase Inhibitors and Methods of Use

Small molecule xanthine oxidase inhibitors are provided, as well as methods for their use in treating gout or hyperuricemia. 115-. (canceled)18. The method of claim 16 , wherein the compound is administered orally.21. The method of wherein the compound is administered orally. This application claims priority to U.S. Provisional Application No. 61/734,409, filed Dec. 7, 2012, which is incorporated herein by reference in its entirety.Gout is caused by hyperuricemia, namely, abnormally high levels of uric acid in the blood. Gout is usually present as acute inflammatory arthritis, as well as tophi, kidney stones, or urate nephropathy. Gout affects 1-2% of adults in developed countries and represents the most common case of inflammatory arthritis in men. In the United States, gouty arthritis accounts for millions of outpatient visits annually. Furthermore, gout and hyperuricemia are associated with chronic diseases such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease.Xanthine oxidase (XO) is a form of a molybdoflavin protein, xanthine oxidoreductase (XOR). It plays an important role in the catabolism of purines in humans, as it catalyzes the oxidation of hypoxanthine to xanthine and then catalyzes the oxidation of xanthine to uric acid. Meanwhile, reactive oxygen species (ROS), including superoxide and HO, are generated during this process. Uric acid can serve as an antioxidant to prevent macromolecular damage by ROS. However, overproduction of uric acid can cause hyperuricemia and lead to gout and other diseases. Therefore, maintaining uric acid at normal levels represents an important therapeutic goal for the prevention of gout and related disorders. For most patients with primary gout, overproduction of uric acid is the primary cause of hyperuricemia.Currently, two drugs have been developed to treat gout. Allopurinol is the most commonly used therapy for chronic gout and has been used clinically for more than 40 years. ...

PROCESSES FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The disclosure provides processes for synthesizing compounds for use as CFTR modulators.

DEHYDROXYLATION OF NITROALCOHOLS TO NITROALKANES

The present invention provides a process for producing nitroalkanes by dehydroxylation of nitroalcohols. This provides an alternate reaction route for making nitroalkanes, such as 2-nitropropane and its derivatives.

PROCESS FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The invention provides a process for the preparation of a compound of Formula 1,

Recyclable chiral catalyst for asymmetric nitroaldol reaction and process for the preparation thereof

The present invention relates to preparation of highly efficient chiral recyclable homogeneous catalysts generated in situ by the reaction of chiral oligomeric [H 4 ] ligands and a metal salt taken in 1:1 molar ratio for asymmetric nitroaldol reaction, wherein nitroaldol reactions of various aldehydes such as aromatic, aliphatic α,β-unsaturated aldehydes, alicyclic aldehydes and nitroalkenes were carried out to produce optically active β-nitroalcohols in high yield and with moderate to excellent enantioselectivity (ee up to >95%) in presence of a base and an optically active chiral recyclable homogeneous catalyst represented by the following formula (I).

Catalyst and Method for Producing Optically Active Anti-1,2-Nitroalkanol Compound

A catalyst, which is obtained by mixing a compound expressed by the following Structural Formula (1), a nitroalkane compound, a neodymium-containing compound, a sodium-containing compound, and a carbon structure: 2. The catalyst according to claim 1 , wherein the nitroalkane compound is a compound represented by the following General Formula (1):{'br': None, 'sup': '1', 'sub': 2', '2, 'R—CH—NO\u2003\u2003General Formula (1)'}{'sup': '1', 'where Rrepresents an alkyl group which has 1 to 20 carbon atoms and may have a substituent.'}3. The catalyst according to claim 1 , wherein the nitroalkane compound is nitroethane.4. The catalyst according to claim 1 , wherein the carbon structure is carbon nanotube.5. The catalyst according to claim 1 , wherein the neodymium-containing compound is NdO(OCH(CH)).6. The catalyst according to claim 1 , wherein the sodium-containing compound is sodium bis(trimethylsilyl)amide.7. The catalyst according to claim 1 , wherein the catalyst is obtained by: mixing the compound expressed by the Structural Formula (1) claim 1 , the neodymium-containing compound claim 1 , the sodium-containing compound claim 1 , and the carbon structure; and after the mixing claim 1 , further mixing the nitroalkane compound.9. The method according to claim 8 , wherein the nitroalkane compound is a compound represented by the following General Formula (1):{'br': None, 'sup': '1', 'sub': 2', '2, 'R—CH—NO\u2003\u2003General Formula (1)'}{'sup': '1', 'where Rrepresents an alkyl group which has 1 to 20 carbon atoms and may have a substituent.'}10. The method according to claim 8 , wherein the nitroalkane compound is nitroethane.11. The method according to claim 8 , wherein the carbon structure is carbon nanotube.12. The method according to claim 8 , wherein the neodymium-containing compound is NdO(OCH(CH)).13. The method according to claim 8 , wherein the sodium-containing compound is sodium bis(trimethylsilyl)amide.14. The method according to claim 8 , wherein the ...

Process

There is disclosed a process for the preparation of a compound of structure (I) ##STR1## in which n is 1 to 3 and each group R is hydrogen or C 1-4 alkyl, which comprises, reaction of compound of structure (II) ##STR2## (prepared by esterifying the hydroxyl compound) in which R 1 is C 1-4 alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR 2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.

Method for preparing 5-substituted oxazoles

The invention provides a method for the preparation of 5-substituted oxazoles in high yield using inexpensive, widely available reagents. The method is particularly useful in the preparation of intermediates necessary in the synthesis of a class of IMPDH inhibitors, in particular VX-497, which is currently in clinical trials. The invention also provides compounds that represent novel intermediates useful in the methods of this invention.

Photocrosslinkable materials

A diamine compound of formula (I) is proposed as well as polymers, copolymers, polyamic acids, polyamic acid esters, or polyimides based on such compound.

New diphenylpyrrole derivatives useful for control of animal pests, e.g. in protection of plants, goods and materials and in veterinary medicine

2,5-Diphenyl-3,4-dihydro-2H-pyrrole derivatives (I) are new. Aminoketones (VIII) and nitroketones (XVIII) used in their preparation are also new. 2-(2-Chlorophenyl)-5-(substituted phenyl)-3,4-dihydro-2H-pyrrole derivatives (I) are new: Ar = group of formula (a): m = 0-4; R<1> = halo; CN; (alkyl)3Si; CONR<4>R<5>; tetrahydropyranyl; -X-A; -B-Z-D; or -Y-E; R<2> = H; halo; CN; NO2; alkyl, haloalkyl, alkoxy, haloalkoxy; alkoxyalkoxy; or -S(O)oR<3>; o = 0-2; R<3> = alkyl or haloalkyl; R<4> and R<5> = H; alkyl; haloalkyl; or phenyl or phenylalkyl optionally substituted with W<1>; X = direct bond; O; S; C(O); C(O)O; OC(O); alkylene; alkenylene; alkynylene; alkyleneoxy; oxyalkylene; thioalkylene; alkylenedioxy; or dialkylsilylene; A = phenyl, naphthyl or tetrahydronaphthyl optionally substituted with W<1>; or aromatic heterocyclyl optionally substituted with W<2>; B = p-phenylene optionally substituted with W<1>; Z = O or S; D = H; alkyl; alkenyl; alkynyl; haloalkyl; haloalkenyl; cycloalkyl or cycloalkylalkyl optionally substituted with halo, alkyl or optionally halo-substituted alkenyl, phenyl or styryl; optionally halo- or alkyl-substituted cycloalkenyl or cycloalkenylalkyl; phenylalkyl, naphthylalkyl, tetrahydronaphthyl or heteroaryl optionally substituted with 6 groups; -C(O)R<6>; -C(O)NR<7>R<8>; or a group of formula (b): -(CH2)p-(CR<9>R<10>)q-(CH2)r-G (b) or Z and G together form phenoxyalkyl optionally substituted with 6 groups; Y = direct bond; O; S; C(O); C(O)O; OC(O); alkylene; alkenylene; alkynylene; alkyleneoxy; oxyalkylene; thioalkylene; alkylenedioxy; or p-phenylene optionally substituted with W<1>; E = H; alkyl; alkenyl; alkynyl; haloalkyl; haloalkenyl; cycloalkyl optionally substituted with 8 groups; cycloalkenyl optionally substituted with halo or alkyl; phenyl optionally substituted with W<1>; heteroaryl optionally substituted with W<2>; ...

2-(2-chlorophenyl)-3,4-dihydro-2h-pyrrol derivatives

The invention relates to novel 2-(2-chlorophenyl)-3,4-dihydro-2H-pyrrol derivatives of formula (I) in which Ar represents substituted phenyl. The invention also relates to a number of methods for producing said derivatives and to their use as pesticides.

process for preparing 2- (3-pyrazolyloxymethylene) nitrobenzene derivatives.

Method of producing nitroalkanol derivatives

The invention relates to nitroalkanol derivatives of the general formula (I), <IMAGE> (I) wherein R1 is a C2-12 alkenyl or alkadienyl group, a C4-12 alkoxyalkyl or alkoxyalkenyl group having one or more C1-3 alkyl substituents, a C3-6 cycloalkyl or cycloalkenyl group, a furyl group, a nitrofuryl group, or a phenyl group having optionally one or more identical or different substituents selected from the group consisting of hydroxy, C1-4 alkoxy, halogen, nitro, C1-4 alkylenedioxy and C1-4 alkenoyloxy groups, R2 and R4 each represent hydrogen or they form together a valence bond, R3 is a C1-12 alkanoyloxy group, a benzoyloxy group having optionally one or more halogen substituents or hydrogen atom, and R5 is a C1-12 alkyl group or a phenyl group having optionally one or more halogen substituents, with the proviso that if R2 and R4 each stand for hydrogen, R1 is other than unsubstituted phenyl and R3 may represent only a C1-4 alkanoyloxy group or a benzoyloxy group having optionally one or more halogen substituents, and with the further proviso that if R2 and R4 form together a valence bond and R5 is methyl, R1 is other than unsubstituted phenyl. The nitroalkenol derivatives defined above as well as the known 1-phenyl-2-nitro-3-acetoxy-propane-1 possess valuable pesticidal effects, primarily fungicidal activities, and can be applied to advantage in the agriculture as plant protecting agents.

The method of obtaining 2-nitrobenzaldehyde

一种乙氧氟草醚的合成方法

本发明涉及一种乙氧氟草醚的合成方法，包括以下步骤：(1)将3、4‑二氯三氟甲苯、氢氧化钾和叔丁醇按照摩尔比：1～1.5：3～5：2～4进行反应，在极性溶剂中脱氯得到含2‑氯‑4‑三氟甲基苯酚钾的混合液，降温抽滤后对混合液减压处理；(2)向混合液中加入碳酸钾，升温同时滴加2、4‑二卤代硝基苯，碳酸钾、2、4‑二卤代硝基苯和3、4‑二氯三氟甲苯的摩尔比为1～1.5：1：2～2.3，保温反应后抽滤，加入甲苯溶解滤液中的2、4‑双(2‑氯‑4‑三氟甲基)苯氧基硝基苯；(3)混合液升温至30℃后向溶液中滴加醇钾保温反应，乙醇、氢氧化钾和2、4‑二卤代硝基苯的摩尔比为4～5：1.2～1.4：1，从反应后的混合液中提取乙氧氟草醚。本发明通过新的合成方法，显著降低了乙氧氟草醚的合成成本。

一种硝基苯乙酮的制备方法

本发明公开了一种硝基苯乙酮的制备方法，以硝基苯甲酸为原料，通过酰氯化、缩合、水解三步反应得到目标产物。该方法反应条件温和、后处理简单，避免了传统方法中涉及的硝化和氧化反应条件苛刻的问题，同时具有污染小、产率高等优点。

Method of preparing nitroacetic or substituted carboxylic acids

1495245 Carboxylation process MONTEDISON SpA 24 March 1976 [28 March 1975] 11916/76 Heading C2C A process for carboxylating a ketone, ester, nitroparaffin or nitrile substrate comprises reacting said substrate with CO 2 and an alkali metal phenate in a linear or cyclic ester, cyclic ether, cyclic sulphone, tertiary aliphatic or cycloaliphatic amine or a saturated or unsaturated heterocyclic base. The preferred reaction temperature is 40‹ to 60‹ C. The phenate may be prepared in situ from the corresponding phenol and alkali metal hydroxide and the water formed being eliminated azeotropically with excess solvent.

Methods for the preparation of benzophenone derivatives

The method of obtaining-nitroketone

The preparation method of cylite containing substituent group

本发明涉及化工技术领域，针对对设备腐蚀严重的问题，提供了一种含取代基的溴化苄的制备方法，该技术方案如下：在55‑70℃，两相条件下，以溴化盐为溴源，以氯气为氧化剂，以偶氮二异丁腈为引发剂，在助剂和催化剂存在下，将含取代基的甲苯溴化为取代溴苄，将物料降温至20‑40℃下静置分层后中和，二次分层后得到取代溴苄溶液。以不挥发，刺激性极低的溴化盐为溴源，通过氯气氧化使得溴重生，提高了溴元素的利用率，反应可快速发生，不存在累计现象，减少对设备腐蚀的情况，降低了工业生产的风险，使得生产过程较为安全。

Microwave synthesis method of 2-nitro-3',4',5'-trifluoro-1,1'-biphenyl

本发明提供了一种2-硝基-3’,4’,5’-三氟-1,1’-联苯的微波合成方法，其包括：将邻硝基氯苯和3,4,5-三氟苯硼酸溶于溶剂中，并加入催化剂和碱均匀混合，之后置于微波反应器中进行反应，再经纯化处理获得2-硝基-3’,4’,5’-三氟-1,1’-联苯；其中所述催化剂采用钯/石墨系催化剂。本发明工艺简单易实施，反应条件温和，原料廉价易得，且反应速度快，产率高，节能环保，利于工业化大规模实施。

Process for preparing phenethanol ethers

Substituted phenethanol ethers are prepared by the etherification of corresponding substituted phenethyl alcohols with an aliphatic primary alcohol. The etherification is carried out by reacting a substituted phenethyl alcohol with an aliphatic primary alcohol in the presence of an acid catalyst.

Process

A kind of synthetic method of adjacent nitro benzyl chloride

本发明公开了一种邻硝基氯苄的合成方法，在邻硝基甲苯中加入催化剂，加热搅拌，并缓慢通入氯气，待反应结束后，回收邻硝基甲苯，获得邻硝基氯化苄。本发明克服了现有邻硝基溴化苄合成方法中热氯化法和光照法存在的产率小、副产物多等缺陷，在邻硝基甲苯中加入催化剂，加热搅拌后通入氯气，待反应结束后，回收处理邻硝基甲苯，得到邻硝基氯化苄，该合成反应可获得纯度≥99%和产率≥80%的产品（以实际消耗的邻硝基甲苯计），高于热氯化法和光氯化法。

Novel synthesis process of o-nitrobenzyl bromide

本发明涉及了一种邻硝基溴苄的新合成工艺，在40％氢溴酸、30％双氧水和引发剂偶氮二异丁腈存在条件下，以邻硝基甲苯为原料，通过自由基溴代反应合成邻硝基溴苄，其中，在该工艺中使用30％双氧水作为氧化剂，通过氧化氢溴酸来提供溴素，并通过严格地调控试验条件使邻硝基甲苯自由基溴代反应具有选择性，合成工序可控，没有二溴代物的生成，同时因产率远高于现有技术水平，且生产成本低、利于环保，是目前适用于工业大规模生产的理想方法。

Process

PCT No. PCT/GB91/00587 Sec. 371 Date Oct. 14, 1992 Sec. 102(e) Date Oct. 14, 1992 PCT Filed Apr. 15, 1991 PCT Pub. No. WO91/16306 PCT Pub. Date Oct. 31, 1991.There is disclosed a process for the preparation of a compound of structure (I) <IMAGE> (I) in which n is 1 to 3 and each group R is hydrogen or C1-4 alkyl, which comprises, reaction of compound of structure (II) <IMAGE> (II) (prepared by esterifying the hydroxyl compound) in which R1 is C1-4alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.

An improved process for the preparation of substituted indolone derivatives

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R1 is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR¿2? in which R is as described for structure (I), and optionally thereafter forming a salt.

An improved process for the preparation of substituted indolone derivatives

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R1 is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR¿2? in which R is as described for structure (I), and optionally thereafter forming a salt.

Improved process for producing substituted indolone derivatives

An improved process for the preparation of substituted indol one derivatives

일반식 (II)의 화합물을 아민 HNR 2 와 반응시킴을 특징으로 하여, 일반식 (I) 및 임의의 이의 염을 제조하는 방법. A process for preparing general formula (I) and any salts thereof, characterized by reacting a compound of general formula (II) with amine HNR 2 . 상기식에서, In the above formula, n은 1 내지 3 이고, n is 1 to 3, 그룹 R은 각각 수소 또는 알킬이고, Group R is each hydrogen or alkyl, R 1 은 알킬, 페닐 또는 치환된 페닐이다. R 1 is alkyl, phenyl or substituted phenyl.

Improved process for preparation of substituted indolone derivatives

制备结构式(I)化合物或其盐的方法，其特征在于使结构式(II)化合物与胺HNR 2 (其中R与结构式(I)中的相同)反应，接着随意地生成盐， 式I和II中n是1至3；R是氢或C 1-4 烷基；R 1 是C 1-4 烷基、苯基或取代的苯基。

An improved process for the preparation of substituted indolone derivatives.

A process for the preparation of a compound of structure (i)in which n is 1 to 3 and each group r is hydrogen or c1-4alkyl, which comprises, reaction of a compound of structure (ii)in which r1 is c1-4alkyl, phenyl or substituted phenyl and n is 1 to 3, with an anime hnr2 in which r is as described for structure (i), and optionally thereafter forming a salt.

An improved process for the preparation of substituted indolone derivatives

An improved process for the preparation of substituted indolone derivatives

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R1 is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt.

An improved process for the preparation of substituted indolone derivatives

AN IMPROVED METHOD FOR PRODUCING SUBSTITUTED INDOLONE DERIVATIVES

"Improved Process for Preparation of Substituted Indolone Derivatives"

AN IMPROVED PROCEDURE FOR THE PREPARATION OF SUBSTITUTED DERIVATIVES FROM INDOLONA.

UN PROCESO PARA LA PREPARACION DE UN COMPUESTO CON LA ESTRUCTURA (I), EN LA QUE N ES DE 1 A 3 Y CADA GRUPO R ES HIDROGENO O ALQUILO, QUE COMPRENDE LA REACCION DE UN COMPUESTO CON LA ESTRUCTURA (II), EN LA QUE R1 ES ALQUILO, FENILO O FENILO SUBSTITUIDO Y N ES DE 1 A 3, CON UNA AMINA HNR2 EN LA QUE R ES LO DESCRITO PARA LA ESTRUCTURA (I) Y, OPCIONALMENTE, LA FORMACION DE UNA SAL CON EL MISMO. A PROCESS FOR THE PREPARATION OF A COMPOUND WITH STRUCTURE (I), IN WHICH N IS 1 TO 3 AND EACH GROUP R IS HYDROGEN OR RENT, WHICH INCLUDES THE REACTION OF A COMPOUND WITH STRUCTURE (II), IN WHICH R1 IS RENT, PHENYL OR SUBSTITUTED PHENYL AND N IS 1 TO 3, WITH AN AMINE HNR2 IN WHICH R IS DESCRIBED FOR THE STRUCTURE (I) AND, OPTIONALLY, THE FORMATION OF A SALT WITH THE SAME.

Improved process for the preparation of 4- [2- (di-n-propylamino) ethyl] -1,3-dihydro-2H-indol-2-one and new intermediate

An improved process for the preparation of substituted indolone derivatives

PCT No. PCT/GB91/00587 Sec. 371 Date Oct. 14, 1992 Sec. 102(e) Date Oct. 14, 1992 PCT Filed Apr. 15, 1991 PCT Pub. No. WO91/16306 PCT Pub. Date Oct. 31, 1991.There is disclosed a process for the preparation of a compound of structure (I) <IMAGE> (I) in which n is 1 to 3 and each group R is hydrogen or C1-4 alkyl, which comprises, reaction of compound of structure (II) <IMAGE> (II) (prepared by esterifying the hydroxyl compound) in which R1 is C1-4alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.

An improved process for the preparation of substituted indolone derivatives

An improved method for producing substituted indolone derivatives

A találmány tárgya javítőtt eljárás (I) általánős képletűszűbsztitűált indőlőnszármazékők előállítására – ahől n = 2, és Rhidrőgénatőm vagy 1–4 szénatőmős alkilcsőpőrt, őly módőn, hőgy egy(II) általánős képletű vegyületet – ahől n = 2, és R1 1–4 szénatőmősalkil-, fenil- vagy szűbsztitűált fenil-, előnyösen p-tőlilcsőpőrt –egy HNR2 általánős képletű aminnal – a képletben R jelentése a fenti –reagáltatnak, majd kívánt setben sót képeznek. A vegyületek agyógyászatban használhatók fel, példáűl a Parkinsőn-kór kezelésérealkalmasak. ŕ

Process

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R<1> is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt.

Esters of 4-hydroxyalkyl-indolin-2-ones

PCT No. PCT/GB91/00587 Sec. 371 Date Oct. 14, 1992 Sec. 102(e) Date Oct. 14, 1992 PCT Filed Apr. 15, 1991 PCT Pub. No. WO91/16306 PCT Pub. Date Oct. 31, 1991.There is disclosed a process for the preparation of a compound of structure (I) (I) in which n is 1 to 3 and each group R is hydrogen or C1-4 alkyl, which comprises, reaction of compound of structure (II) (II) (prepared by esterifying the hydroxyl compound) in which R1 is C1-4alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.

PROCESS FOR THE PREPARATION OF SUBSTITUTED INDOLONE DERIVATIVES

An improved proces for the preparation of substituted indoline derivatives

AN IMPROVED PROCESS FOR THE PREPARATION OF SUBSTITUTED INDOLINE DERIVATIVES WHICH DERIVATIVES WHICH PROVIDES IN A FIRST ASPECT, A PROCESS FOR THE PREPARATION OF A COMPOUND OF STRUCTURE (1)(FORMULA 1)IN WHICH N IS 1 TO 3 AND EACH GROUP E IS HYDROGEN OR C1-C4 ALKYL, WHICH COMPRISES, REACTION OF A COMPOUND OF STRUCTURE (II)(FORMULA 2)IN WHICH IS 1 TO 3 AND R1 IS C1-C4 ALKYL, PHENYL OR SUBSTITUTED PHENYL WITH AN AMINE OF STRUCTURE HNR2 WHERE R IS AS DESCRIBED FOR STRUCTURE (I), AND OPTIONALLY THEREAFTER FORMING A SALT.

Improved process for the preparation of substituted indolone derivatives and intermediates in the preparation thereof

Process for the preparation of 4-(aminoalkyl)-1,3-dihydro-2h-indol-2-one derivatives, and intermediates therefor

Method of obtaining substituted derivatives of indole

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R<1> is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt.

PROCESS OF PREPARATION OF SUBSTITUTED DERIVATIVES OF INDOLONE AND ITS INTERMEDIARIES

An improved process for the preparation of substituted indolone derivatives

Process for the preparation of indolones and intermediates therefor

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R<1> is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. [WO9116306A1]

4-hydroxyalkyl-indol-2-ones

A process for the preparation of a compound of structure (I), in which n is 1 to 3 and each group R is hydrogen or alkyl, which comprises, reaction of a compound of structure (II), in which R<1> is alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. [WO9116306A1]

Esters of 2-substituted phenyl alkyl alcohols

PCT No. PCT/GB91/00587 Sec. 371 Date Oct. 14, 1992 Sec. 102(e) Date Oct. 14, 1992 PCT Filed Apr. 15, 1991 PCT Pub. No. WO91/16306 PCT Pub. Date Oct. 31, 1991.There is disclosed a process for the preparation of a compound of structure (I) (I) in which n is 1 to 3 and each group R is hydrogen or C1-4 alkyl, which comprises, reaction of compound of structure (II) (II) (prepared by esterifying the hydroxyl compound) in which R1 is C1-4alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.

Intermediates useful in the preparation of substituted indolone derivatives