Separating agent for optical isomers

To provide a novel separating agent for optical isomers based on a polymer having an optically active moiety, provided is a separating agent for optical isomers formed of: a helical polymer obtained by using an aromatic isonitrile as a monomer having an amide group in which an optically active amino acid is amide-bonded to an aromatic ring; and a carrier for carrying the helical polymer by being chemically bonded to an end of the helical polymer.

METHOD OF RESOLUTION OF (RS)- 1,1'-BI-2-NAPHTHOL FOR OBTAINING ENANTIOMERIC PURE I.E. (S)-(-)-1,1'-BI-2-NAPHTHOL AND/OR (R)-(+)-1,1'-BI-2-NAPHTHOL VIA CO-CRYSTAL FORMATION WITH OPTICALLY ACTIVE DERIVATIVES OF y -AMINO ACIDS

Novel method for synthesis of optically pure (S)-(−)-1,1′-bi-2-naphthol and/or (R)-(+)-1,1′-bi-2-naphthol via resolution of racemic (RS)-1,1′-bi-2-naphthol through formation of co-crystal with optically active derivatives of γ-amino acids.

Novel Process for the Preparation of Nitrogen Substituted Aminotetralins Derivatives

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

NOVEL SYNTHETIC APPROACH TO beta-AMINOBUTYRYL SUBSTITUTED COMPOUNDS

The present invention relates to process to prepare β-aminobutyryl compounds having β-amino acid core structural moieties and optionally having γ-phenyl and/or heterocyclic structural moieties. Such compounds are useful as key structure framework of modern drug chemistry. 9. The process according to claim 1 , wherein in (v) the nitro group is converted into an amino group by contacting with a reducing agent claim 1 , which is selected from elemental metals in the presence of acids claim 1 , wherein the elemental metals are selected from zinc and tin claim 1 , cations in low oxidation states selected from Fe(II) claim 1 , Sn(II) claim 1 , Cr (II) claim 1 , hydrogen sulfide claim 1 , metal sulfides and polysulfides claim 1 ,or by catalytic hydrogenation in the presence of a metal catalyst, selected from nickel, palladium, rhodium, iridium, gold and platinum, to give the final compound of formula (I).15. The process according to claim 1 , wherein the compound of formula (VIIIa) or (XIIa) is subjected to reduction by a reductase claim 1 , selected from reductase enzymes derived from Actinomyces claim 1 , Saccharomyces or Bacteria gens Clostridium.19. The process according to claim 18 , wherein the desired separated enantiomer of the compound of the formula (IX) is the (R)-enantiomer claim 18 , and the undesired separated enantiomer of the compound of the formula (IX) is the (S)-enantiomer.20. The process according to claim 18 , wherein the racemisation of the separated undesired enantiomer is carried out in the presence of acid claim 18 , base or a mixture of acid and base claim 18 , wherein the acid is in molar excess in respect to the base.21. The process according to claim 20 , wherein the acid is selected from inorganic acid claim 20 , organic acid or the mixture thereof.22. The process according to claim 20 , wherein the base is selected from inorganic base claim 20 , organic base or the mixture thereof.24. (canceled)25. (canceled)26. (canceled)27. (canceled)28. A ...

New process for the resolution of enantiomers of (3,4 dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile and application in the synthesis of ivabradine

Process for the optical resolution of the compound of formula (I): by chiral chromatography. Application in the synthesis of ivabradine, of its addition salts with a pharmaceutically acceptable acid and of their hydrates.

Process to purify dialkyl sulfides

The invention relates to new processes to prepare low odor dialkyl sulfides, the low odor dialkyl sulfides obtainable by these processes and to methods of using these low odor dialkyl sulfides. Moreover, the invention relates to a process to prepare dialkyl sulfide borane complexes of high purity, the dialkyl sulfide borane complexes obtainable by this process and to a process for enantioselective reductions employing these dialkyl sulfide borane complexes of high purity as reducing agent.

Triazole compound and use thereof

In order to provide a compound that shows a strong effect on controlling a plant disease, a triazole compound of the present invention (i) is a compound in which —OH group, —R 2 group, and CH 2 —Ar group are bonded in cis configuration with a cyclopentane, (ii) is (−)-enantiomer or (+) enantiomer, and (iii) is represented by Formula (I): (wherein R 1 represents an alkyl group; R 2 represents a haloalkyl group; and Ar represents a substituted/unsubstituted aromatic hydrocarbon group or a substituted/unsubstituted aromatic heterocyclic group.

Chiral Separation System

A system for separation of enantiomers includes a column packed with a stationary phase; a magnetic field generator generating a magnetic field, within which the column is placed, and the magnetic field interacts with the enantiomers as the enantiomers elute through the column with a mobile phase; and a control unit, in communication with the magnetic field generator and the column, to adjust the strength and direction of the magnetic field to separate the enantiomers. 1. A system for separation of enantiomers , comprising:a column packed with a stationary phase;a magnetic field generator to generate a magnetic field, within which the column is placed, and the magnetic field interacting with the enantiomers as the enantiomers elute through the column with a mobile phase; anda control unit in communication with the magnetic field generator and the column to adjust the strength and direction of the magnetic field to separate the enantiomers.2. The system of claim 1 , wherein the magnetic field generator comprises at least one solenoid claim 1 , at least one permanent magnet claim 1 , a superconducting magnet claim 1 , or any other suitable magnetic field generator.3. The system of claim 1 , wherein the magnetic field is a static magnetic field.4. The system of claim 1 , wherein the strength of the magnetic field is adjusted to induce a magnetic dipole in each of the enantiomers and to align the induced magnetic dipole with the magnetic field.5. The system of claim 1 , wherein the direction of the magnetic field is adjusted by varying an angle or a distance claim 1 , or both thereof claim 1 , between the magnetic filed and the column.6. The system of claim 1 , wherein the stationary phase comprises a ferromagnetic material.7. The system of claim 6 , wherein the ferromagnetic material comprises FeOnanocrystals having a size of smaller than 1000 nm.8. The system of claim 1 , wherein the column is a C18 claim 1 , monolithic claim 1 , ion exchange claim 1 , hydrophilic ...

METHODS FOR CHIRAL RESOLUTION OF TROLOX

The invention relates to methods of separating Trolox isomers (R)-Trolox and (S)-Trolox, comprising: (a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(−)-2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and (b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent. 1. A method of separating Trolox isomers (R)-Trolox and (S)-Trolox , comprising:(a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(+2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and(b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent.2. The method of claim 1 , wherein step (a) comprises dissolving the mixture of (R) and (S)-Trolox and the resolving agent in a solvent.39.-. (canceled)10. The method of claim 2 , wherein the solvent is ethyl acetate.1114.-. (canceled)15. The method of claim 2 , wherein about 4 to about 6 volumes of solvent are added in step (a).1618.-. (canceled)19. The method of claim 1 , wherein about 0.95 to about 1.20 equivalents of resolving agent are used in step (a).2022.-. (canceled)23. The method of claim 1 , wherein the mixture in step (a) is seeded with the desired solid salt.24. The method of claim 1 , wherein step (b) comprises filtering the solid salt.25. The method of claim 24 , wherein step (b) further comprises a step (b)(1) claim 24 , comprising slurrying the solid salt in the solvent.26. The ...

STEREOISOMER OF FLOCOUMAFEN, COMPOSITION AND RODENTICIDE BAIT COMPRISING SAME, AND METHOD FOR CONTROLLING TARGET RODENT PESTS

Disclosed is a configurational stereoisomer, referred to as enantiomer E, of flocoumafen, the enantiomer Ehaving, as determined by the chromatographic analysis of flocoumafen including four configurational stereoisomers of flocoumafen, carried out under conditions described hereinafter, a retention time twith a value such that t Подробнее

POROUS CHIRAL MATERIALS AND USES THEREOF

A porous chiral material of formula [M(L)(A)]Xwherein M is a metal ion; L is a nitrogen-containing bidentate ligand; A is the anion of mandelic acid or a related acid; and Xis an anion 1. A porous chiral material of formula [M(L)(A)]X wherein M is a metal ion; L is a nitrogen-containing bidentate ligand; A is the anion of mandelic acid or a related acid; and X is an anion.2. A porous chiral material according to wherein M is selected from a group consisting of: cobalt claim 1 , chromium claim 1 , iron claim 1 , nickel claim 1 , manganese claim 1 , calcium claim 1 , magnesium claim 1 , cadmium claim 1 , copper and zinc.3. A porous chiral material according to wherein L is selected from a group consisting of: 4 claim 1 ,4′-bipyridine claim 1 , 1 claim 1 ,2-bis(4-pyridyl)ethane claim 1 , and 4 claim 1 ,4′-bipyridylacetylene.4. A porous chiral material according to wherein A is the anion of (S)-(−)-mandelic acid.5. A porous chiral material according to wherein X is a triflate ion.6. (canceled)7. A material of formula [M(L)(A)]XGwherein M is a metal ion; L is a nitrogen-containing bidentate ligand; A is an anion of mandelic acid or a related acid; X is an organic anion; G is a guest molecule; and n is from 0 to 5.8. (canceled)9. A crystalline sponge comprising a porous chiral material of formula [M(L)(A)]X.10. A method of separating enantiomers claim 1 , the method comprising contacting a composition comprising a mixture of enantiomers with a material of .11. (canceled)12. A method of separating enantiomers according to claim 10 , the method comprising passing a composition comprising the mixture of enantiomers through a chromatography column comprising as a stationary phase a chiral porous material of formula [M(L)(A)]X wherein M is a metal ion; L is a nitrogen-containing bidentate ligand; A is an anion of mandelic acid or a related acid; and X is an anion.13. A method of separating enantiomers according to claim 12 , the method comprising:{'sub': '1.5', 'sup': +', '−, ...

Chiral separation and analysis by molecular propeller effect

A method and a device for separation and analysis of chiral molecules are described. The method relies on using a fluid shear to induce molecular rotation and the molecular propeller effect to transform rotational motion into translation motion of opposite direction for counterpart enantiomers. The direction of motion of each enantiomers is used to determine its absolute configuration by comparing the direction value with theoretically calculated one. The device uses multiple moving surfaces or pressure induced flows to induce shear flow condition in the solution to separate enantiomers.

PROCESS FOR PREPARING (CYCLOPENTYL[d]PYRIMIDIN-4-YL)PIPERAZINE COMPOUNDS

The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes. 2. The process of claim 1 , wherein the cyclization is achieved by contacting the compound or salt of Formula VIwith a formamidine salt.3. The process of claim 1 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 1 , or salts thereof claim 1 , with a nitrilase enzyme or a lipase enzyme.4. The process of claim 3 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 3 , or salts thereof claim 3 , with a nitrilase enzyme.5. The process of claim 3 , wherein the enzymatic resolution is achieved by contacting the isomeric mixture comprising the compound of Formula VIand Formula VI claim 3 , or salts thereof claim 3 , with a lipase enzyme.6. The process of any one of to claim 3 , wherein the steps (ii) and (iii) are performed through-process.7. The process of claim 1 , wherein step (ii) is performed at a pH of about 7.8. The process of claim 1 , wherein step (ii) is performed at a pH of about 9. This application is a continuation of U.S. patent application Ser. No. 15/514,188, filed Mar. 24, 2017, which is a national phase entry of International Patent Application No. PCT/US2015/052143, filed Sep. 25, 2015, which claims the benefit of priority U.S. Provisional Application No. 62/055,893, ...

PROCESS FOR THE PREPARATION OF EXAMETAZIME

The present invention provides an improved process for the preparation of exametazime, which is used as ligand in preparation of technetium-99m complex. 6. The process according to any of the preceding claims , wherein the dehydrating agents is selected from calcium hydride , molecular sieves , magnesium sulphate and sodium sulphate.7. The process according to any of the preceding claims , wherein the chiral resolving acid is selected from L-(+) tartaric acid , D-(−) tartaric acid , L-malic acid , D-malic acid , S-(+) mandelic acid , R-(−) mandelic acid , S-(+)-O-acetyl mandelic acid , R-(−)-O-acetyl mandelic acid , (−)-naproxen , (+)-naproxen , (1R)-(−)-camphor sulfonic acid , (1S)-(+)-camphor sulfonic acid , (1R)-(+)-bromocamphor-10-sulfonic acid , (1S)-(−)-bromocamphor-10-sulfonic acid , (−)-Dibenzoyl-L-tartaric acid , (−)-Dibenzoyl-L-tartaric acid monohydrate , (+)-Dibenzoyl-D-tartaric acid , (+)-Dibenzoyl-D-tartaric acid monohydrate , (+)-dipara-tolyl-D-tataric acid , (−)-dipara-tolyl-L-tataricacid , L(−)-pyroglutamic acid , L(+)-pyroglutamic acid , (+)-lactic acid , (−)-lactic acid , (S)-(+)-2-chloromandelic acid , (R)-(+2-chloromandelic acid.8. The process according to any of the preceding claims , wherein the and ‘l’ mixture of chiral resolving acid is selected from (±) tartaric acid , (±) malic acid , (±) ascorbic acid , (±) mandelic acid , (±)-O-acetyl mandelic acid , (±) naproxen , (±) camphor sulfonic acid , (±) bromocamphor-10-sulfonic acid , (±) Dibenzoyl-tartaric acid , (±) dipara-tolyl-tataric acid , (±) pyroglutamic acid , (±) lactic acid , (±)-2-chloromandelic acid.9. The process according to any of the preceding claims , wherein the suitable bases is selected from sodium hydroxide , potassium hydroxide , sodium carbonate , potassium carbonate , sodium bicarbonate , potassium bicarbonate , either alone or as their aqueous solutions.10. The process according to any of the preceding claims , wherein the suitable solvents is selected from nitriles , ...

POLYMORPHIC AND AMORPHOUS FORMS OF (R)-2-HYDROXY-2-METHYL-4-(2,4,5-TRIMETHYL-3,6-DIOXOCYCLOHEXA-1,4-DIENYL)BUTANAMIDE

Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms. 1. A polymorph of a solvate of (R)-2-hydroxy-2-methyl-4-(2 ,4 ,5-trimethyl-3 ,6-dioxocyclohexa-1 ,4-dienyl)butanamide , wherein the polymorph is selected from the group consisting of Forms IV , V , and VI wherein a powder X-ray diffraction pattern for polymorph Form IV comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2: 4.31 , 12.97 , and 13.20; wherein a powder X-ray diffraction pattern for polymorph Form V comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2: 9.61 , 11.49 , and 15.45; and wherein a powder X-ray diffraction pattern for polymorph Form VI comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2: 6.27 , 9.91 , and 12.94.26.-. (canceled)7. The polymorph of claim 1 , wherein the polymorph is Form V.8. The polymorph of claim 1 , wherein the polymorph is Form V claim 1 , wherein a powder X-ray diffraction pattern for the polymorph comprises characteristic peaks at the following angular positions claim 1 , wherein the angular positions may vary by ±0.2: 9.61 claim 1 , 11.49 claim 1 , 12.93 claim 1 , 15.45 claim 1 , and 26.05.9. (canceled)10. A composition comprising the polymorph claim 7 , wherein the composition is essentially free of Forms I-IV and VI claim 7 , wherein; wherein a powder X-ray diffraction pattern for polymorph Form I comprises characteristic peaks at least at the ...

SALTS OF COMPOUNDS HAVING A BENZIMIDAZOLIC STRUCTURE, USES AND PROCESS FOR THE PREPARATION THEREOF

The present invention relates to salts of anthelmintic compounds with a benzimidazolic structure, such as albendazole (ABZ), fenbendazole (FBZ), triclabendazole (TRBZ), or sulphoxides thereof, flubendazole (FLZ), mebendazole (MBZ), oxibendazole (OBZ), thiabendazole (TBZ), cambendazole (CBZ), parbendazole (PBZ), nocodazole (NCZ), the use thereof and a process for preparation thereof. 1) Salts of benzimidazolic compounds with metals selected in the group consisting of lithium , sodium , potassium , magnesium and calcium , said benzimidazolic compounds being selected in the group consisting of albendazole , fenbendazole , triclabendazole , flubendazole , mebendazole , oxibendazole , thiabendazole , cambendazole , parbendazole , nocodazole , albendazole sulphoxide , fenbendazole sulphoxide and triclabendazole sulphoxide , said sulphoxides being in racemic form or in the form of the R- or S-enantiometer.2) Pharmaceutical composition comprising or consisting of at least one salt as defined in claim 1 , as an active ingredient claim 1 , together with one or more excipients and/or adjuvants.3) Pharmaceutical composition according to claim 2 , further comprising at least one drug selected of the group consisting in anthelmintics claim 2 , antitumourals and proton pump inhibitors.4) Pharmaceutical composition according to claim 3 , wherein said at least one anthelmintic drug is selected in the group consisting of abamectin claim 3 , praziquantel claim 3 , diethylcarbamazine claim 3 , niclosamide claim 3 , ivermectin claim 3 , suramin claim 3 , pirantel claim 3 , levamisole claim 3 , octadepsipeptides such as emodepside claim 3 , aminoacetonitrile derivatives such as monepantel claim 3 , and spiroindoles such as derquantel.5Vinca) Pharmaceutical composition according to claim 3 , wherein said at least one antitumour drug is selected in the group consisting of taxanes such as paclitaxel claim 3 , docetaxel and cabazitaxel claim 3 , camptothecins such as irinotecan and topotecan ...

Configurational stereoisomer of difethialone, composition and rodenticide bait comprising same, and method for controlling target rodent pests

Disclosed is a laevorotatory enantiomer of the configurational stereoisomer of difethialone, named homo-stereoisomer, the formula of which is 3-(4′-bromobiphenyl-4-yl)-1-(4-hydroxythiocoumarin-3-yl)-1,2,3,4-tetrahydronaphthalene, in which carbons 1 and 3 of the 1,2,3,4-tetrahydronaphthalene group have the same absolute configuration.

POLYELECTROLYTE COMPLEXES

The present invention relates to aqueous compositions of associative polyelectrolyte complexes (PECs), optionally containing surfactants, biocidal agents and/or oxidants, which can provide a cleaning benefit and surface protection to treated articles including reduced soiling tendency, reduced cleaning effort and improved soil repellency, as well as providing bacteriostatic properties to treated surfaces that thereby gain resistance to water, environmental exposure and microbial challenge. Treatment means and compositions are provided that employ associative polyelectrolyte complexes formed by combining a water soluble cationic first polyelectrolyte with a water soluble second polyelectrolyte bearing groups of opposite charge to the first polyelectrolyte under suitable mixing conditions and at least one oxidant selected from the group: alkaline metal salts and/or alkaline earth metal salts of hypochlorous acid, hypochlorous acid, solubilized chlorine, any source of free chlorine, acidic sodium chlorite, active chlorine generating compound and any combinations or mixtures thereof. Also provided are means to form stable associative polyelectrolyte complexes with at least one oxidant in aqueous solutions having R values from about 0.10 to 20. 1. A treatment composition comprising:(i) water;(ii) an amphoteric surfactant;(iii) at least one water-soluble associative polyelectrolyte complex comprising a water soluble cationic first polyelectrolyte; and a water soluble second polyelectrolyte bearing groups of opposite charge to said first polyelectrolyte; wherein the resulting water-soluble associative polyelectrolyte complex is non-precipitating in the treatment composition, wherein R, the molar ratio of charged groups present on said first polyelectrolyte to oppositely charged groups present on said second polyelectrolyte is from about 0.10 to 20;(iv) wherein said cationic first polyelectrolyte and said second polyelectrolyte each comprise at least one of homopolymers, ...

ANTIFUNGAL COMPOUND PROCESS

The present invention relates to a process for preparing a compound of 5 or 5*, or a mixture thereof, that is useful as an antifungal agent. In particular, the invention seeks to provide new methodology for preparing compounds 7 or 7* and 11 or 11* and substituted derivatives thereof. 4. The process of claim 3 , wherein M is Mg or MgX claim 3 , and X is halogen.8. The process of claim 1 , further comprising enriching the enantiomeric purity of an enantiomeric compound mixture of Formula 7 and 7* and/or enriching the enantiomeric purity of an enantiomeric compound mixture of Formula 11 and 11* claim 1 , comprising: 'the suitable solvent or solvent mixture is selected from acetonitrile, isopropanol, ethanol, water, methanol, or combinations thereof;', '(i) crystallizing said enantiomeric compound mixture with a chiral acid in a suitable solvent or solvent mixture, wherein(ii) isolating the enantio-enriched chiral salt mixture; and(iii) free-basing the enantio-enriched chiral salt mixture to provide the enantio-enriched compound mixture.9. The process of claim 8 , further comprising reslurrying the enantio-enriched chiral salt mixture in a slurrying solvent or slurrying solvent mixture.10. The process of claim 8 , wherein the suitable solvent or solvent mixture is (a) acetonitrile or (b) a mixture of acetonitrile and methanol.11. The process of claim 9 , wherein the slurrying solvent or slurrying solvent mixture is (a) acetonitrile or (b) a mixture of acetonitrile and methanol.12. The process of claim 10 , wherein the mixture of acetonitrile and methanol comprises 80-90% acetonitrile and 10-20% methanol.13. The process of claim 11 , wherein the mixture of acetonitrile and methanol comprises 80-90% acetonitrile and 10-20% methanol.14. The process of claim 8 , wherein the chiral acid is selected from the group consisting of tartaric acid claim 8 , di-benzoyltartaric acid claim 8 , malic acid claim 8 , camphoric acid claim 8 , camphorsulfonic acid claim 8 , ascorbic acid ...

STEREODYNAMIC CHEMOSENSORS

The present invention relates to multifunctional chemosensors that can measure the concentration, enandomeric excess (ee), and absolute configuration of chiral compounds. The chemosensors described herein may contain a backbone moiety that is bonded to a fluorescent moiety and a moiety for bonding a chiral compound. Backbone moieties may include aromatic groups, for example, naphthyl. The chemosensors described herein are useful for measuring concentration, enandomeric excess, and absolute configuration of organic molecules in areas such as high throughput screening. 2. The compound of ; wherein{'sup': 1', '5, 'Rand Rare independently hydrogen or methyl;'}{'sup': 2', '4', '2', '4, 'sub': 1', '6, 'Rand Rare independently hydrogen, —CHO, or —(CO)(C-C) alkyl, wherein at least one Rand Ris not hydrogen.'}{'sup': 3', '9, 'claim-text': {'sup': '9', 'sub': 1', '6, 'wherein Ris hydrogen, (C-C) alkyl, or aryl;'}, 'Ris NH(R) or OH,'}{'sup': '6', 'Ris hydrogen or methyl;'}{'sup': 7', '8, 'Rand Rare hydrogen; and'} 'wherein the aryl or heteroaryl group may be substituted or unsubstituted.', 'Z is an aryl or heteroaryl group,'}3. The compound of ; wherein Z is anthracene claim 1 , a quinoline N-oxide claim 1 , an isoquinoline N-oxide claim 1 , or a pyridyl-N-oxide.4. The compound of ; wherein Z is isoquinoline N-oxide or 4′-pyridyl-N-oxide.7. The chemosensor of ; wherein Z is achiral or undergoes fast racemization and/or diastereomerization.8. The chemosensor of ; wherein Z is achiral undergoes fast racemization and/or diastereomerization.9. A method of providing stereoselective recognition of a stereoisomer of a chiral compound;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein the method comprises combining a compound of formula (I) from with a sample comprising the chiral substrate compound as a mixture of stereoisomers, and'}wherein the compound of formula (I) preferentially binds the stereoisomer to form an adduct.10. The method of ; wherein the method further ...

Process for electrochemical separation of enantiomers of an amino acid from a racemic mixture

The process comprises electrolyzing the first electrolyte having 1 molar solution of lithium perchlorate and 0.01 molar solution of racemic mixture of amino acid in an electrochemical cell containing a working electrode having polycrystalline metal surface configured to adsorb L-enantiomer of amino acid using a saw-tooth current. Further, the polarity of the saw-tooth current is reversed to de-adsorb the L-enantiomer of amino acid from the working electrode into the second electrolyte re-filled in the cell. The process of the present disclosure to separate enantiomer of amino acid from a racemic mixture is simple and economical.

STEREOCHEMICALLY DEFINED POLYPROPIONATES AND METHODS FOR MAKING AND USING THE SAME

The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries. 23-. (canceled)7. (canceled)957-. (canceled)60. The compound of claim 1 , wherein R is —C(O)Rand Ris substituted with —COOH.64. The process of claim 63 , wherein the reducing agent is a hydride.65. The process of claim 63 , wherein the reducing agent is sodium borohydride.66. The process of claim 63 , wherein the acid is hydrochloric acid.68. The process of claim 67 , further comprising claim 67 , prior to reacting the racemic mixture of phthalates of Formulas 2A and 2B with the first chiral amine in the solvent to form the pair of diastereomeric salts thereof in the solution claim 67 , dissolving the racemic mixture of phthalates of Formulas 2A and 2B in the solvent.69. The process of claim 68 , wherein the racemic mixture of phthalates of Formulas 2A and 2B are dissolved in the solvent at a volume ratio in a range of about 1:12 to about 1:20 (phthalates:solvent).70. The process of claim 67 , wherein the solvent is acetone.71. The process of claim 67 , wherein the first chiral amine is (S)-α-methylbenzylamine. This application is a divisional of and claims priority to pending U.S. Utility patent application Ser. No. 15/906,401 which is a divisional of and claims priority to pending U.S. Utility patent application Ser. No. 15/501,658, which was the U.S. national phase under 35 U.S.C. § 371 of PCT International Patent Application Serial No. PCT/US2015/043535, filed on Aug. 4, 2015, which claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/032,757, filed Aug. 4, 2014, the disclosure of which is hereby incorporated by reference herein in its entirety.The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically ...

Process for the separation of enantiomers of piperazine derivatives

The invention relates to a process for preparing either enantiomer of a compound of formula (I), wherein X, Y and n have the meaning given in claim 1, with high enantiomeric excess (e.e.), by chiral resolution in the presence of a non-racemic, chiral acid.

A NOVEL CHIRAL POLYMER FOR ENANTIOSELECTIVE SEPARATION AND PROCESS FOR PREPARATION THEREOF

The present invention relates to a novel polyfluorene appended with protected glutamic acid of Formula (I) for heterogeneous enantioselective separation and sensing of amino acids, amino alcohol, hydroxyl acid, sugar, aromatic drug and ascorbic acid from racemic mixture in water and process for preparation thereof. The present invention further provides a process for separation of enantiomers and diastereomers into their individual isomers using a polyfluorene compounds of Formula (I). 2. The polymer as claimed in claim 1 , wherein R is glutamic acid.3. The polymer as claimed in claim 1 , wherein said polymer is polyfluorene appended with dicarboxylic amino acid for heterogeneous enantioselective separation and sensing of amino acids claim 1 , amino alcohol claim 1 , hydroxyl acid claim 1 , sugar claim 1 , aromatic drugs and ascorbic acid from racemic mixture in water.4. The polymer as claimed in claim 1 , wherein said polymer transforms from a helix form to β-sheet in water.5. A process of preparation of polymer of Formula I comprising the steps of:a) preparing a reaction mixture of 2,7-dibromofluorene, 6-bromohexan-1-ol and tetrabutyl ammonium chloride in toluene or DMSO.b) adding sodium hydroxide to the reaction mixture of step (a) followed by heating the mixture at the temperature ranging from 120° C. to 130° C. under argon atmosphere for 12 to 20 h to afford 2,7-dibromo-9,9-di-n-hexanolfluorene;c) esterifying 2,7-dibromo-9,9-di-n-hexanolfluorene using 4-dimethyl amino pyridine and boc-L-glutamic acid-1-tert butyl ester in presence of dicyclohexylcarbodiimide to afford (S)-1-tert-butyl-5-(6-(2,7-dibromo-9-(6-(((R)-5-(tert-butoxy)-4-((tert-butoxycarbonyl)amino)-5- oxopentanoyl)oxy)hexyl)-9H-fluoren-9-yl)hexyl)2-((tert-butoxycarbonyl)amino)pentanedioate;{'sub': 3', '4, 'd) adding potassium carbonate to the reaction mixture comprising product of step (c), 1,4-benzene diboronic ester and Pd(PPh)in THF followed by refluxing at a temperature ranging from 65° C. to 70° ...

Method for the production of lumateperone and its salts

Method for the production of formula (I) lumateperone or its acid addition salts so that the enantiomer compound with stereochemistry 6bR,10aS is separated form the cis racemate using resolution and the formula (II) stereoisomer is alkylated with 4-halo-4′-fluoro butyrophenone (X═I, Br, Cl) to produce the formula (I) lumateperone, or optionally its acid addition salt. The object of the invention also relates to the amorphous form of the morphologically uniform p-toluenesulfonic acid salt of lumateperone and to the naphthalene-2-sulfonic acid salt of lumateperone, to the 1:2 stoichiometry salt of lumateperone formed with naphthalene-2-sulfonic acid.

SYNTHETIC ROUTE TO 2'-DEOXY-2',2'-DIFLUOROTETRAHYDROURIDINES

The present invention relates to methods and intermediates for synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine compounds. 2. The method of claim 1 , wherein the catalyst is a Bronsted-Lowry base.3. The method of claim 1 , wherein the catalyst is about 1 mol % to about 20 mol % 1 claim 1 ,8-diazabicyclo(5.4.0)undec-7-ene (DBU).4. The method of claim 1 , wherein the catalyst is about 5 mol % to about 10 mol % DBU.5. The method of claim 4 , wherein the catalyst is about 5 mol % DBU.6. The method of claim 1 , wherein the catalyst is acetic acid claim 1 , trifluoroacetic acid claim 1 , diisopropylethylamine claim 1 , or ammonium hydroxide.7. The method of claim 1 , wherein the solution comprises acetonitrile.8. The method of claim 1 , wherein the solution comprises acetone claim 1 , tetrahydrofuran claim 1 , DMSO claim 1 , or methanol.10. The method of claim 9 , wherein the catalyst is about 1 mol % to about 20 mol % DBU11. The method of claim 10 , wherein the catalyst is about 5 mol % to about 10 mol % DBU.12. The method of claim 11 , wherein the catalyst is about 5 mol % DBU.13. The method of claim 9 , wherein the catalyst is acetic acid claim 9 , trifluoroacetic acid claim 9 , diisopropylethylamine claim 9 , or ammonium hydroxide.14. The method of claim 9 , wherein the final product is recrystallized or slurrified.15. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetonitrile.16. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetone or tetrahydrofuran.17. The method of claim 9 , wherein step (b) is carried out in the presence of CeCl.18. The method of claim 9 , further comprising a step of reducing the particle size of compound 1.19. The method of claim 18 , wherein the particle size is reduced to about 50 μm or less.2030-. (canceled) This application is a continuation application of and claims priority to U.S. patent application Ser. No. 15/027,022, filed Apr. ...

ENANTIOMERS OF SPIRO-OXINDOLE COMPOUNDS AND THEIR USES AS THERAPEUTIC AGENTS

This invention is directed to the (S)-enantiomer of the compound of formula (I): 2. The method of wherein the disease or condition is pruritus. This application is a divisional application of U.S. patent application Ser. No. 14/510,634, filed Oct. 9, 2014 (now allowed); which is a divisional application of U.S. patent application Ser. No. 13/619,915, filed Sep. 14, 2012 (now U.S. Pat. No. 8,883,840); which is a divisional application of U.S. patent application Ser. No. 12/825,168, filed Jun. 28, 2010 (now U.S. Pat. No. 8,450,358); which claims the benefit under 37 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61/221,424, filed Jun. 29, 2009.This invention is directed to a specific enantiomer of a spiro-oxindole compound, specifically to the enantiomers use in human or veterinary therapeutics for treating diseases or conditions in a mammal, preferably a human, which are ameliorated or alleviated by the modulation, preferably inhibition, of voltage-gated sodium channels.PCT Published Patent Application No. WO 2006/110917, the disclosure of which is incorporated in full by reference herein, discloses certain spiro-oxindole compounds, in particular, 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, i.e., the compound of the following formula (I):These compounds are disclosed therein as being useful in treating diseases or conditions, such as pain, in mammals, preferably humans, which are ameliorated or alleviated by the modulation, preferably inhibition, of voltage-gated sodium channels.The present invention is directed to the discovery that the (S)-enantiomer and the (R)-enantiomer of the following compound of formula (I):demonstrate a difference in potency for the inhibition of voltage-gated sodium channel activity.Accordingly, in one aspect, the invention provides the (S)-enantiomer of 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, i.e., the (S)- ...

Process of separating chiral isomers of chroman compounds and their derivatives and precursors

The present invention relates to a process of separating chiral isomers of chroman compounds, particularly tocopherols and tocotrienols as well as the esters and intermediates thereof. It has been found that this process allows a separation of the desired isomer with a higher yield and enables the use of the non-desired isomers in a very efficient way. Said process is particularly useful when implemented in an industrial process. Furthermore, it has been found that this process allows using isomer mixtures as they result from traditional industrial synthesis.

PREPARATION METHOD OF 1-PALMITOYL-3-ACETYLGLYCEROL, AND PREPARATION METHOD OF 1-PALMITOYL-2-LINOLEOYL-3-ACETYLGLYCEROL USING SAME

Disclosed are a method for preparing 1-palmitoyl-3-acetylglycerol in high purity and high yield without a purification process using a column chromatography, and a method for preparing 1-palmitoyl-2-linoleoyl-3-acetylglycerol in high purity and high yield using the same as a key intermediate. The method for preparing 1-palmitoyl-3-acetyl glycerol comprises the steps of: forming a reaction mixture including 1-palmitoyl-3-acetyl glycerol of the Formula 1 in the specification by reacting 1-palmitoylglycerol of the Formula 2 in the specification and an acetylating agent; and separating the optically active 1-palmitoyl-3-acetylglycerol by crystallizing the reaction mixture in a saturated hydrocarbon solvent having 5 to 7 carbon atoms. 18-. (canceled)9. A method of making 1-palmitoyl-3-acetylglycerol comprising the steps of:reacting 1-palmitoylglycerol with an acetylating agent, andseparating the 1-palmitoyl-3-acetylglycerol thus formed by crystallization,wherein the 1-palmitoylglycerol and 1-palmitoyl-3-acetylglycerol are racemic or optically active compounds.10. The method of claim 9 , wherein the acetylating agent is selected from the group consisting of acetylchloride claim 9 , acetylbromide and the mixtures thereof.11. The method of wherein the amount of the acetylating agent is 1.3 to 1.4 molar equivalents relative to the 1-palmitoylglycerol.12. The method of claim 9 , wherein the reaction of 1-palmitoylglycerol and the acetylating agent is carried out in a solvent and in the presence of an organic base claim 9 , wherein the solvent is a non-polar claim 9 , aprotic solvent.13. The method of claim 12 , wherein the organic base comprises pyridine.14. The method of claim 12 , wherein the non-polar claim 12 , aprotic solvent comprises one or more of a solvent selected from dichloromethane claim 12 , acetone claim 12 , ethyl acetate claim 12 , and mixtures of any of these.15. The method of claim 15 , wherein the solvent comprises dichloromethane.16. The method of claim 9 ...

ANTIFUNGAL COMPOUND PROCESS

The present invention relates to a process for preparing compound 1 that is useful as an antifungal agent. In particular, the invention seeks to provide new methodology for preparing compound 1 and substituted derivatives thereof. 4. The process of any one of - , wherein forming the trimethylsilyl-cyanohydrin is performed in the presence of a chiral catalyst.8. The process of claim 7 , wherein Z is phenyl claim 7 , p-tolyl claim 7 , methyl claim 7 , or ethyl.9. The process of claim 7 , wherein the crystallization solvent or crystallization solvent mixture is ethyl acetate claim 7 , isopropyl acetate claim 7 , ethanol claim 7 , methanol claim 7 , or acetonitrile claim 7 , or combinations thereof.10. The process of claim 7 , wherein the crystallization co-solvent or crystallization co-solvent mixture is pentane claim 7 , methyl tert-butylether claim 7 , hexane claim 7 , heptane claim 7 , or toluene claim 7 , or combinations thereof.11. The process of claim 7 , wherein forming the trimethylsilyl-cyanohydrin is performed in the presence of a chiral catalyst.12. The process of claim 11 , further comprising enriching the enantiomeric purity of amino-alcohol 1-6 or 1-7 to afford enantio-enriched amino-alcohol 1-6* or 1-7*.13. The process of claim 7 , further comprising enriching the enantiomeric purity of amino-alcohol 1-6 or 1-7 to afford enantio-enriched amino-alcohol 1-6* or 1-7*. This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/955,633 filed Mar. 19, 2014, which is expressly incorporated by reference herein.This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this invention.The present invention relates to a process for preparing compound 1 that is useful as an antifungal agent. In particular, the invention seeks to provide a new ...

Method for producing optically active substance, optically active substance, method for producing chiral molecule, and chiral molecule

Provided is a method for producing an optically active substance, the method including an asymmetric induction, wherein an asymmetry inducer is allowed to act on a chiral molecule having a half-life of enantiomeric excess of shorter than 10 hours, thereby increasing abundance of one enantiomer of the chiral molecule. According to this method, one enantiomer of a chiral molecule that is susceptible to racemization can be selectively and efficiently obtained.

METHOD OF PREPARING (3R,4S)-3-ACETAMIDO-4-ALLYL-N-(TERT-BUTYL)PYRROLIDINE-3-CARBOXAMIDE

A method is provided to conveniently separate racemic (3R,4S)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide and (3S,4R)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide using selective crystallization with chiral carboxylic acids. 2. The amine compound of claim 1 , wherein Ris tert-butyl.3. The amine compound of either or claim 1 , wherein Ris —CHCH═CH.4. The amine compound of any of - claim 1 , wherein Ris H.5. The amine compound of any of - claim 1 , wherein Ris acetyl or trifluoroacetyl.6. The amine compound of any of - claim 1 , wherein X is NH.7. The amine compound of any of - claim 1 , wherein X is O.9. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 80% ee.10. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 90% ee.11. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 95% ee.12. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 97% ee.13. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 99% ee.14. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of between 80% and 99.5% ee.15. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of between 90% and 99.5% ee.17. The salt of claim 16 , wherein Aand Aare phenyl.18. The salt of or claim 16 , wherein Ais substituted by one Rand Ais substituted by one R.20. The salt of any one of - claim 16 , wherein the amine compound in the salt has an enantiomeric excess of at least 75% ee.21. The salt of claim 20 , wherein the carboxylic acid compound in the salt is essentially a single enantiomer.22. The salt of any one of - claim 20 , wherein Ris tert-butyl.23. The salt of any one of - ...

COFORMER SALTS OF (2S,3S)-METHYL 7-FLUORO-2-(4-FLUOROPHENYL)-3-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-4-OXO-1,2,3,4-TETRAHYDROQUINOLINE-5-CARBOXYLATE AND METHODS OF PREPARING THEM

Described herein are coformer salts of (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate optionally as a solvate and additionally optionally as a hydrate, including crystalline forms, and methods of preparing the (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-teirahydroquinoline-5-carboxylate optionally as a coformer salts. 1. A coformer salt of (2S ,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1 ,2 ,4-triazol-5-yl)-4-oxo-1 ,2 ,3 ,4-tetrahydroquinoline-5-carboxylate optionally as a solvate and additionally optionally as a hydrate thereof.2. The coformer salt of claim 1 , wherein the coformer salt is in a substantially pure crystalline form.3. The coformer salt of claim 1 , wherein the coformer salt is a [(1S)-endo]-(+)-3-bromo-10-camphor sulfonic acid salt of (2S claim 1 ,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)-4-oxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinoline-5-carboxylate.4. The coformer salt of claim 1 , wherein the coformer salt is a crystalline form exhibiting at least one of:{'sup': '13', 'a solid state C NMR spectrum with peaks at 210.3, 25.3, 21.8, 20.8, 19.5, and 18.5 ppm±0.2 ppm;'}a differential scanning calorimetry thermogram having a broad endotherm between 25° C. and 90° C. and an endotherm with a maximum between about 135° C. and 147° C.;a thermogravimetric analysis thermogram indicative of a solvated material; ora X-ray powder diffraction pattern comprising peaks at 2θ angle degrees ±0.2 2θ angle degrees of 6.7, 9.7, 18.5, 19.5, and 22.5. The coformer salt of claim 1 , wherein the coformer salt is in a crystalline form exhibiting at least one of:{'sup': '13', 'a solid state C NMR spectrum with peaks at 210.3, 25.3, 21.8, 20.8, 19.5, and 18.5 ppm±0.2 ppm; or'}a X-ray powder diffraction pattern comprising peaks at 2θ angle degrees ±0.2 2θ angle degrees of 6.7, 9.7 ...

OPTICALLY ACTIVE PYRANOCHROMENYL PHENOL DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

The present invention relates to pyranochromenylphenol derivatives having different efficacies depending on the direction of optical activity and a pharmaceutical composition including the same, and in the pyranochromenylphenol derivatives, an R-enantiomer has excellent anti-diabetic efficacy by suppressing a rise in blood sugar and an S-enantiomer has excellent anti-obesity efficacy by suppressing an increase in body weight. 2. The method of claim 1 ,wherein:{'sub': '1', 'Ris methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, or 2-ethylbutyl;'}{'sub': '2', 'Ris a hydrogen atom; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}3. The method of claim 1 ,wherein:{'sub': '1', 'Ris methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, or 2-ethylbutyl;'}{'sub': '2', 'Ris methyl or methoxy; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}6. The method of claim 5 ,wherein:{'sub': '1', 'Ris methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, and 2-ethylbutyl;'}{'sub': '2', 'Ris a hydrogen atom; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}7. The method of claim 5 ,wherein:{'sub': '1', 'Ris methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, and 2-ethylbutyl;'}{'sub': '2', 'Ris methyl or methoxy; and'}{'sub': 3', '4, 'Rand Rare each methyl.'} This application is a Continuation of U.S. patent application Ser. No. 16/313,777, filed Dec. 27, 2018, which is a 35 U.S.C. § 371 national stage application of PCT International Application No. PCT/KR20171006863, filed Jun. 29, 2017, which claims priority from ...

BROMOTRIAZOLE INTERMEDIATES

Bromotriazole intermediates are useful in the synthesis of agonists of the APH receptor. Such compounds include those selected from This application is a continuation of, and claims priority to, U.S. patent application Ser. No. 16/033,632, filed on Jul. 12, 2018, which is a continuation of, and claims priority to, U.S. patent application Ser. No. 15/629,567, filed on Jun. 21, 2017, now U.S. Pat. No. 10,058,550, which is a continuation of, and claims priority to, U.S. patent application Ser. No. 15/297,487, filed on Oct. 19, 2016, now U.S. Pat. No. 9,745,286, which is a divisional of, and claims priority to, U.S. patent application Ser. No. 15/158,174, filed on May 18, 2016, now U.S. Pat. No. 9,573,936, which claims priority to U.S. Provisional Application No. 62/164,106, filed on May 20, 2015, each of which is hereby incorporated by reference in its entirety and for all purposes as if fully set forth herein.The present invention relates to compounds capable of acting as agonists of the APJ Receptor, and compositions that include compounds that are agonists of the APJ Receptor. The compounds and compositions may be used to activate the APJ Receptor and to treat various disease conditions. An example of one area where such compounds may be used is in the treatment of cardiovascular conditions. In particular, the compounds may be used to improve contractility and ejection fraction in subjects with chronic heart failure and may be used to treat patients with heart failure with reduced ejection fraction and patients with heart failure with preserved ejection fraction.Apelin is the endogenous ligand for APJ (APLNR, angiotensin receptor like-1). The APJ receptor is a member of the rhodopsin-like G protein-coupled receptor (GPCR) family. The apelin/APJ system has been observed in many tissues such as heart, kidney, pancreas, lung and the central nervous system. This suggests diverse roles of the system in the physiology and pathology of mammals.Apelin peptides are processed ...

Coformer salts of (2s,3s)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1h-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate and methods of preparing them

Described herein are coformer salts of (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate optionally as a solvate and additionally optionally as a hydrate, including crystalline forms, and methods of preparing the (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate optionally as a coformer salts.

POLYMORPHIC AND AMORPHOUS FORMS OF (R)-2-HYDROXY-2-METHYL-4-(2,4,5-TRIMETHYL-3,6-DIOXOCYCLOHEXA-1,4-DIENYL)BUTANAMIDE

Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms. 1. (canceled)2125.-. (canceled)126. A composition comprising a polymorph of an anhydrate , a hydrate , or a solvate of (R)-2-hydroxy-2-methyl-4-(2 ,4 ,5-trimethyl-3 ,6-dioxocyclohexa-1 ,4-dienyl)butanamide , wherein the composition comprises a polymorph Form I and at least one polymorph selected from the group consisting of II , Form III , Form IV , Form V , and Form VI;wherein a powder X-ray diffraction pattern for polymorph Form I comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 12.06, 15.33, 17.03, and 17.26;wherein a powder X-ray diffraction pattern for polymorph Form V comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 9.61, 11.49, 12.93, and 15.45;wherein a powder X-ray diffraction pattern for polymorph Form III comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 9.16, 14.02, 15.23, and 21.10;wherein a powder X-ray diffraction pattern for polymorph Form II comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 9.63, 10.85, 11.33, and 19.33;wherein a powder X-ray diffraction pattern for polymorph Form IV comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 4.31, 8.76, 12.97, and 13.20; andwherein a powder X-ray diffraction pattern for polymorph ...

POLYELECTROLYTE COMPLEXES

The present invention relates to aqueous compositions of associative polyelectrolyte complexes (PECs), optionally containing surfactants, biocidal agents and/or oxidants, which can provide a cleaning benefit and surface protection to treated articles including reduced soiling tendency, reduced cleaning effort and improved soil repellancy, as well as providing bacteriostatic properties to treated surfaces that thereby gain resistance to water, environmental exposure and microbial challenge. Treatment means and compositions are provided that employ associative polyelectrolyte complexes formed by combining a water soluble cationic first polyelectrolyte with a water soluble second polyelectrolyte bearing groups of opposite charge to the first polyelectrolyte under suitable mixing conditions and at least one oxidant selected from the group: alkaline metal salts and/or alkaline earth metal salts of hypochlorous acid, hypochlorous acid, solubilized chlorine, any source of free chlorine, acidic sodium chlorite, active chlorine generating compound and any combinations or mixtures thereof. Also provided are means to form stable associative polyelectrolyte complexes with at least one oxidant in aqueous solutions having R values from about 0.10 to 20. 1. A treatment composition comprising:(i) water;(ii) citric acid in an amount of from 0.075% to 1.25%;(iii) at least one water-soluble associative polyelectrolyte complex comprising a water soluble cationic first polyelectrolyte; and a water soluble second polyelectrolyte bearing groups of opposite charge to said first polyelectrolyte; wherein the resulting water-soluble associative polyelectrolyte complex is non-precipitating in the treatment composition, wherein R, the molar ratio of charged groups present on said first polyelectrolyte to oppositely charged groups present on said second polyelectrolyte is from about 0.10 to 20;(iv) wherein said cationic first polyelectrolyte and said second polyelectrolyte each comprise at least ...

METHOD OF PREPARING (3R,4S)-3-ACETAMIDO-4-ALLYL-N-(TERT-BUTYL)PYRROLIDINE-3-CARBOXAMIDE

A method is provided to conveniently separate racemic (3R,4S)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide and (3S,4R)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide using selective crystallization with chiral carboxylic acids. 2. The amine compound of claim 1 , wherein Ris tert-butyl.3. The amine compound of either or claim 1 , wherein Ris —CHCH═CH.4. The amine compound of any of - claim 1 , wherein Ris H.5. The amine compound of any of - claim 1 , wherein Ris acetyl or trifluoroacetyl.6. The amine compound of any of - claim 1 , wherein X is NH.7. The amine compound of any of - claim 1 , wherein X is O.9. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 80% ee.10. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 90% ee.11. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 95% ee.12. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 97% ee.13. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of greater than 99% ee.14. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of between 80% and 99.5% ee.15. The amine compound of any one of - claim 1 , wherein the amine compound has an enantiomeric excess of between 90% and 99.5% ee.17. The salt of claim 16 , wherein Aand Aare phenyl.18. The salt of or claim 16 , wherein A is substituted by one Rand Ais substituted by one R.20. The salt of any one of - claim 16 , wherein the amine compound in the salt has an enantiomeric excess of at least 75% ee.21. The salt of claim 20 , wherein the carboxylic acid compound in the salt is essentially a single enantiomer.22. The salt of any one of - claim 20 , wherein Ris tert-butyl.23. The salt of any one of ...

Separation and Manipulation of a Chiral Object

Among other things, for use in directional motion of chiral objects in a mixture, a field is applied across the chamber and is rotating relative to the chamber to cause rotation of the chiral objects. The rotation of the objects causes them to move directionally based on their chirality. The method applies to sugars, proteins, and peptides, among other things, and can be used in a wide variety of applications. 15-. (canceled)6. A method comprisingenhancing a purity of at least one of two enantiomers in a mixture by separating molecules of the two enantiomers in each of a series of chambers, the purity of the enantiomer in at least some of the successive chambers being at increasingly higher levels, andtransferring a portion of at least one of the separated enantiomers from each of the chambers to a previous one or a next one of the chambers in the series.720-. (canceled)21. A method for use with an apparatus that comprisesa chamber to hold a mixture containing one or more enantiomers;a field source to impose a rotating field on the mixture;the chamber having an inlet to receive the mixture, and an outlet to remove a portion of the mixture that contains at least one of the enantiomers in an elevated concentration relative to its average concentration in the mixture in the chamber; anda chemical reaction vessel connected to the chamber to hold fluid to be delivered to the chamber;the method comprisinganalyzing or processing a reaction component in the fluid using the chamber.22. The method of in which the analyzing or processing comprises analyzing purity of a reaction component.23. The method of in which the analyzing or processing comprises purification of a reaction component.24. The apparatus of in which the analyzing or processing comprises determining the absolute configuration of a reaction component.256. The method of in which the chiral objects comprise achiral molecules claim 21 , such as lipids claim 21 , that have chiral labels attached. This application ...

SYNTHETIC ROUTE TO 2'-DEOXY-2',2'-DIFLUOROTETRAHYDROURIDINES

The present invention relates to methods and intermediates for synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine compounds. 18-. (canceled)10. The method of claim 9 , wherein the catalyst is about 1 mol % to about 20 mol % DBU11. The method of claim 10 , wherein the catalyst is about 5 mol % to about 10 mol % DBU.12. The method of claim 11 , wherein the catalyst is about 5 mol % DBU.13. The method of claim 9 , wherein the catalyst is acetic acid claim 9 , trifluoroacetic acid claim 9 , diisopropylethylamine claim 9 , or ammonium hydroxide.14. The method of claim 9 , wherein the final product is recrystallized or slurrified.15. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetonitrile.16. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetone or tetrahydrofuran.17. The method of claim 9 , wherein step (b) is carried out in the presence of CeCl.18. The method of claim 9 , further comprising a step of reducing the particle size of compound 1.19. The method of claim 18 , wherein the particle size is reduced to about 50 μm or less.2030-. (canceled)31. The method of claim 9 , wherein the palladium catalyst is palladium on charcoal. This application is a continuation application of and claims priority to U.S. patent application Ser. No. 15/813,743, filed Nov. 15, 2017, now allowed, which is a continuation application of and claims priority to U.S. patent application Ser. No. 15/027,022, filed Apr. 4, 2016, now U.S. Pat. No. 9,834,576, which is a 35 U.S.C. § 371 national phase application of PCT Application PCT/US2014/062874, filed Oct. 29, 2014 which claims the benefit of U.S. Provisional Application Ser. No. 61/896,703, filed Oct. 29, 2013, the entire contents of which are incorporated by reference herein.The present invention relates to methods and intermediates for synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine compounds.Several important chemotherapeutic ...

A CHIRAL RESOLUTION METHOD MIMICKING MAGNETIC BENEFICIATION AND THE MAGNETIC NANO-INHIBITORS FOR SELECTIVE ENRICHMENT

A core-shell nanocomposite is formed by co-assembly of an amphiphilic polymer and hydrophobically modified magnetic nanoparticles, with its core being a hydrophobically modified magnetic nanomaterial and its shell being the amphiphilic polymer, wherein hydrophilic segments in the amphiphilic polymer are located at an outermost layer of the shell. The above composite can be used as additives in the crystallization of conglomerates and obtain optically pure crystals of both enantiomers in a single process. The key thereof is that the composite is used to enrich molecules with the same configuration while inhibit the crystallization of the other enantiomer in a supersaturated solution of conglomerates, such that a non-magnetic crystal and a magnetic crystal (which are enantiomers of each other) are generated in a unit operation. Optically pure crystals of both enantiomers with over 90 ee % can be obtained by one-time crystallization, and the total yield can be as high as 40%. 1. A core-shell nanocomposite , which is formed by co-assembly of an amphiphilic polymer and hydrophobically modified magnetic nanoparticles , with a hydrophobically modified magnetic nanomaterial as its core and the amphiphilic polymer as its shell , wherein hydrophilic segments in the amphiphilic polymer are located at an outermost layer of the shell.2. The core-shell nanocomposite according to claim 1 , wherein a crosslinking reaction is carried out between the hydrophilic segments to form a cross-linked shell.5. The core-shell nanocomposite according to claim 1 , wherein the magnetic nanomaterial is selected from magnetic nanoparticles formed by the following materials: Fe claim 1 , Co claim 1 , Ni claim 1 , FePt claim 1 , CoPt claim 1 , FeAu claim 1 , FePd claim 1 , SmCo claim 1 , FeO claim 1 , γ-FeO claim 1 , MFeO claim 1 , MO.6FeO claim 1 , and MFeO claim 1 , wherein Min MFeOrepresents Zn claim 1 , Mn claim 1 , Ni claim 1 , or Co claim 1 , and Min MFeOrepresents Ba or Sr;wherein the ...

SEPARATION OF ENANTIOMERS OF 3-ETHYLBICYCLO[3.2.0]HEPT-3-EN-6-ONE

A process to isolate a compound of Formula (2a) or a salt or solvate thereof, comprising a) reacting a mixture of diastereoisomers of Formulae (2a, 2b) with a basic heterocyclic-aldehyde compound and an optically active amine in the presence of a base; and b) separating the compound of Formula (2a) from the product of step a) by acid extraction. The compound of Formula (2a) may be produced with an enantiomeric excess of 98%. Compounds of Formula (2a) are useful intermediates in a process to prepare a bicyclic γ-amino tetrazole derivative of Formula (I) which finds utility in treating neuropathic pain and disorders of the central nervous system. 2. A process according to wherein the compound of Formula 2a is produced with an enantiomeric excess of 98%.4. A process according to claim 3 , wherein the basic heterocyclic-aldehyde compound of Formula 12 is selected from the group consisting of 4-pyridinecarboxalaldehyde claim 3 , 1-methyl-5-imidazolecarboxaldehyde claim 3 , 1-methyl-4-imidazolecarboxaldehyde claim 3 , 3-pyridinecarboxaldehyde and 2-pyridine-carboxaldehyde.5. A process according to claim 4 , wherein the basic heterocyclic-aldehyde compound comprises 4-pyridinecarboxyaldehyde.6. A process according to claim 1 , wherein the optically active amine is a secondary amine.7. A process according to claim 6 , wherein the optically active amine comprises (R)-2-(diphenylmethyl)pyrrolidine.8. A process according to claim 1 , wherein the base is selected from the group consisting of 4-methylmorpholine claim 1 , N claim 1 ,N-diisopropylethylamine claim 1 , trimethylamine claim 1 , tributylamine claim 1 , N-methylpyrrole claim 1 , N-methylpyrolidine claim 1 , N-methylpiperadine claim 1 , pyridine claim 1 , 4-picoline claim 1 , 2 claim 1 ,6-lutidine claim 1 , N-methylimidazole claim 1 , N claim 1 ,N-diethylaniline claim 1 , potassium phosphate and 1 claim 1 ,8-diazobicyclo[5 claim 1 ,4 claim 1 ,0]undec-7-ene and 1 claim 1 ,4-diazobicyclo[2 claim 1 ,2 claim 1 ,2]octane.9. ...

Process for the Separation of Optical Isomers of Racemic 3-Alkylpiperidine-Carboxylic Acid Ethyl Esters

The subject-matter of the invention is process for the separation of optical isomers of racemic 3-alk-3-carboxylic acid ethyl esters of formula rac-I with the resolving agent (II) (−)-2,3:4,5-di-O-izopropylidene-2-keto-L-gulonic acid (hereinafter: diacetone-L-ketogulonic acid). 1. A process for the preparation of the high enantiomerically pure optical isomers ((R)-Ia-c and (S)-Ia-c) of the 3-alkylpiperidine-3-carboxylic acid ethyl esters of formula rac-I (wherein in the formula I the meaning of R can be methyl group (Ia) , ethyl group (Ib) or isopropyl group (Ic)) characterized in that the rac-Ia-c amines are dissolved separately in a suitable organic solvent , preferably in acetone at a temperature between 0° C. and 56° C. , reacted with an amount of 0.8-1.2 molequivalent of (−)-2 ,3:4 ,6-di-O-isopropylidene-2-keto-L-gulonic acid (diacetone-L-ketogulonic acid) resolving agent of formula II , preferably with the monohydrate thereof and after dissolving the resolving agent optionally , the solution is seeded with pure diastereomeric salt prepared from Ia-c enantiomers having appropriate configuration and resolving agent II , then after cooling of the mixture , the diastereomeric salt is separated by filtration and the appropriate high enantiomeric purity (R)-Ia or (R)-Ib or (S)-Ic enantiomers are liberated either from the crystalline (R)-Ia.II or (R)-Ib.II or (S)-Ic.II salts directly or after their recrystallization from an organic solvent , preferably from isopropanol , and optionally obtain therefrom the crystalline (R)-Ia.HCl , (R)-Ib.HCl and (S)-Ic.HCl salts in an organic solvent with hydrochloric acid which are separated by filtration and isolate the high enantiomeric purity crystalline products of (S)-Ia.HCl , (S)-Ib.HCl and (R)-Ic.HCl by the separation from the (S>>R)-Ia.II , (S>>R)-Ia.II and (R>>S)-Ia.II salts remaining in the residues obtained from the filtrate of the diastereomeric salt formation and recrystallization in the same manner as the crystalline ...

Hepatitis c virus inhibitor and uses thereof

Disclosed is a compound of formula (I) as an inhibitor of hepatitis C virus (HCV), or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, usable to treat HCV infections or hepatitis C diseases, and is also useful as an inhibitor of HCV non-structural protein 5A (NS5A).

POLYELECTROLYTE COMPLEXES

The present invention relates to aqueous compositions of associative polyelectrolyte complexes (PECs), optionally containing surfactants, biocidal agents and/or oxidants, which can provide a cleaning benefit and surface protection to treated articles including reduced soiling tendency, reduced cleaning effort and improved soil repellancy, as well as providing bacteriostatic properties to treated surfaces that thereby gain resistance to water, environmental exposure and microbial challenge. Treatment means and compositions are provided that employ associative polyelectrolyte complexes formed by combining a water soluble cationic first polyelectrolyte with a water soluble second polyelectrolyte bearing groups of opposite charge to the first polyelectrolyte under suitable mixing conditions and at least one oxidant selected from the group: alkaline metal salts and/or alkaline earth metal salts of hypochlorous acid, hypochlorous acid, solubilized chlorine, any source of free chlorine, acidic sodium chlorite, active chlorine generating compound and any combinations or mixtures thereof. Also provided are means to form stable associative polyelectrolyte complexes with at least one oxidant in aqueous solutions having R values from about 0.10 to 20. 1. A treatment composition comprising:(i) water;(ii) at least one surfactant;(iii) citric acid;(iv) at least one water-soluble associative polyelectrolyte complex comprising a water soluble cationic first polyelectrolyte; and a water soluble second polyelectrolyte bearing groups of opposite charge to said first polyelectrolyte; wherein the resulting water-soluble associative polyelectrolyte complex is non-precipitating in the treatment composition, wherein R, the molar ratio of charged groups present on said first polyelectrolyte to oppositely charged groups present on said second polyelectrolyte is from about 0.10 to 20;(v) wherein said cationic first polyelectrolyte and said second polyelectrolyte each comprise at least one of ...

Process for obtaining optically active pirlindole enantiomers and salts thereof

The present invention provides a new process for obtaining optically active pirlindole enantiomers, in the form of a free base or in the form of pharmaceutically acceptable salts. The products obtained according to the present invention are enantiomerically pure and are useful in medicine.

SEPARATING AGENT FOR OPTICAL ISOMERS

Provided is a separating agent for optical isomers, which is configured of a novel xylan derivative and a carrier. Specifically provided is a separating agent for optical isomers, which is configured of a carrier and a xylan-phenylcarbamate derivative that is obtained by substituting a hydroxy group of xylan with a group represented by formula (I) or (II). (In formula (I), R1 represents a halogen or an alkyl group having 1-5 carbon atoms; and the position of substitution of the R1 moiety is the meta position or the para position. In formula (II), each of R2 and R3 independently represents a halogen or an alkyl group having 1-5 carbon atoms, and R2 and R3 are groups different from each other.) 2. The separating agent for optical isomers according to claim 1 , wherein the groups that substitute the hydroxyl groups in the xylan are groups represented by formula (I) claim 1 , and Ris an alkyl group having 1 to 5 carbon atoms.3. The separating agent for optical isomers according to claim 2 , wherein the Rsubstitution position is a meta position claim 2 , and Ris a methyl group or an ethyl group.4. The separating agent for optical isomers according to claim 1 , wherein the groups that substitute the hydroxyl groups in the xylan are groups represented by formula (II) claim 1 , and in formula (II) claim 1 , Ris a halogen and Ris an alkyl group having 1 to 5 carbon atoms.5. The separating agent for optical isomers according to claim 4 , wherein Ris chlorine and Ris a methyl group or an ethyl group.6. The separating agent for optical isomers according to claim 1 , wherein the carrier is silica gel. The present invention relates to a separating agent for optical isomers, and specifically relates to a separating agent for optical isomers, which has a structure in which hydroxyl groups in xylan are substituted with carbamate derivatives having specific structures.Optical isomers are used as medicines and raw materials thereof. In such applications that act on living bodies, it ...

METHOD FOR THE PRODUCTION OF PRAZIQUANTEL

The present invention relates to a method for the racemization of enantiomerically pure or enantiomerically enriched Praziquantel under basic conditions and a method for the production of (R)-Praziquantel in enantiopure or enantiomerically enriched form, which comprises the racemization method. 2. A method according to claim 1 , wherein the base is a tertiary alkali alkoxide.3. A method according to claim 2 , wherein the tertiary alkali alkoxide used for the racemization is potassium tert.-butoxide.4. A method according to claim 1 , wherein the racemization is a performed in a dipolar aprotic reaction medium.5. A method according to claim 4 , wherein the dipolar aprotic reaction medium is selected from the group consisting of N-Methyl-2-pyrrolidone claim 4 , dimethylformamide claim 4 , dimethylsulfoxide claim 4 , tetrahydrofuran claim 4 , methyltetrahydrofuran claim 4 , dioxane and mixtures thereof in all ratios.6. A method according to claim 1 , wherein the racemization is performed at a temperature in a range between −50° C. and +40° C.7. A method according to claim 1 , wherein the amount of base used for the racemization is in the range of 0.05 eq to 1.5 eq.8. A method according to claim 1 , wherein:a tertiary alkali alkoxide is used as a base for the racemization;the racemization is performed in a dipolar aprotic reaction medium selected from a group consisting of N-Methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, methyltetrahydrofuran, dioxane and mixtures thereof in all ratios;the amount of base used for the racemization is in the range between 0.05 eq to 1.5 eq;the racemization is performed at a temperature in the range between −50° C. and +40° C.9. A method for the production of (R)-Praziquantel in enantiopure or enantiomerically enriched form claim 1 , comprising following steps:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. Racemization of enantiomerically pure or enantiomerically enriched (S)-Praziquantel according to ; ...

Cinchonium betaine catalysts and methods of using same

Provided herein are cinchonium betaine catalysts and methods of promoting asymmetric imine isomerization reactions using the same. 2: The compound of claim 1 , wherein Rand Rare each phenyl.3: The compound of claim 1 , wherein Ris selected from methoxy claim 1 , t-butoxy and t-butyldimethylsiloxy.4: The compound of claim 1 , wherein Ris —CH═CH.5: The compound of claim 1 , wherein Ris pyrimidinyl substituted with one or more groups selected from aryl and halo.6: The compound of claim 1 , wherein Ris 4-chloro-2 claim 1 ,5-diphenylpyrimidinyl.78-. (canceled)11: The method of claim 10 , wherein Ris alkyl selected from methyl claim 10 , ethyl and n-butyl.12: The method of claim 10 , wherein Ris cyclohexyl.13: The method of claim 10 , wherein Ris phenyl claim 10 , optionally substituted with methyl claim 10 , methoxy or fluoro.14: The method of claim 10 , wherein Ris phenyl substituted with nitro.15: The method of claim 10 , wherein the imine and the at least one compound are contacted in a non-aqueous system in the presence of a base.16: The method of claim 15 , wherein the base is NaOH or KOH.17: The method of claim 15 , wherein the base is NaCOor KCO.18: The method of claim 10 , wherein the amount of the at least one compound ranges from about 0.01 mol % to about 0.1 mol % with respect to the imine.20: The compound of claim 1 , wherein Ris —OH.21: The compound of claim 1 , wherein Ris —OMe. This patent application claims priority to and the benefit of U.S. Patent Application Ser. No. 62/323,426, filed Apr. 15, 2016, the entire contents of which are incorporated herein by reference.This invention was made with government support under grant No. NIH GM-61591 awarded by the National Institutes of Health. The government has certain rights in the invention.Chiral organic catalysts containing both a hydrogen bond donor and an acceptor can facilitate biomimetic 1,3-proton transfer catalysis to promote highly enantioselective olefin and imine isomerizations. These ...

OPTICALLY ACTIVE PYRANOCHROMENYL PHENOL DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

The present invention relates to pyranochromenylphenol derivatives having different efficacies depending on the direction of optical activity and a pharmaceutical composition including the same, and in the pyranochromenylphenol derivatives, an R-enantiomer has excellent anti-diabetic efficacy by suppressing a rise in blood sugar and an S-enantiomer has excellent anti-obesity efficacy by suppressing an increase in body weight. 2. The optically active pyranochromenylphenol compound claim 1 , the pharmaceutically acceptable salt claim 1 , or the solvate thereof of claim 1 ,{'sub': '1', 'wherein Ris ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, or 2-ethylbutyl;'}{'sub': '2', 'Ris a hydrogen atom; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}3. The optically active pyranochromenylphenol compound claim 1 , the pharmaceutically acceptable salt claim 1 , or the solvate thereof of claim 1 ,{'sub': '1', 'wherein Ris ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, or 2-ethylbutyl;'}{'sub': '2', 'Ris methyl or methoxy; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}6. The optically active pyranochromenylphenol compound claim 5 , the pharmaceutically acceptable salt claim 5 , or the solvate thereof of claim 5 ,{'sub': '1', 'wherein Ris ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-ethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, and 2-ethylbutyl;'}{'sub': '2', 'Ris a hydrogen atom; and'}{'sub': 3', '4, 'Rand Rare each methyl.'}7. The optically active pyranochromenylphenol compound claim 5 , the pharmaceutically acceptable salt claim 5 , or the solvate thereof of claim 5 ,{'sub': '1', 'wherein Ris ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl, n-pentyl, 2-methylbutyl, 3- ...

Method for Separating Optically Active Hydroxy Cineole Derivatives

The present invention relates to a method for separating an optically active hydroxy cineole derivatives by lixiviation and crystallization and enantiomerically pure optically active hydroxy cineole derivatives of purity greater than 99.5% that have been prepared by this process. The present invention further relates to use of the desired enantiomer having enantiomeric excess of at least 99.5% ee as prepared according to the present invention, for the synthesis of enantiomerically pure 7-oxabicyclo[2.2.1]heptane derivatives. 113-. (canceled)15. The method of claim 14 , further comprising adding seed crystals of the desired enantiomer in step (ii).16. The method of claim 14 , wherein{'sup': '1', 'sub': 1', '6', '2, 'Ris selected from the group consisting of hydrogen and C-C-alkyl; wherein alkyl is straight-chain or branched, unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of F, Cl, Br, I, CN, NO, methyl, phenyl and benzyl; and'}{'sup': '2', 'sub': 1', '6', '2, 'Ris selected from the group consisting of hydrogen and C-C-alkyl; wherein alkyl is straight-chain or branched, unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of F, Cl, Br, I, CN, NO, methyl, phenyl and benzyl.'}17. The method of claim 16 , wherein Ris methyl and Ris isopropyl.18. The method of claim 14 , wherein the desired enantiomer is either the optically active hydroxy cineole derivative of formula (I-R) or the optically active hydroxy cineole derivative of formula (I-S).19. The method of claim 14 , wherein in step (ii) the suspension is stirred at temperature in the range of ≥10 to ≤120° C.20. The method of claim 14 , wherein in step (iii) the isolation of the crystals of the desired enantiomer is carried out at temperature in the range of ≥−10 to ≤30° C.21. The method of claim 14 , wherein in step (iii) the desired enantiomer is isolated by a method selected from the group consisting of filtration or ...

Method for producing lacosamide and intermediate thereof

The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.

METHOD FOR PRODUCING (R)-1,1,3-TRIMETHYL-4-AMINOINDANE

A method for producing (R)-1,1,3-trimethyl-4-aminoindane includes the following steps (A), (B), and (C). Step (A) is a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane, step (B) is a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane, and step (C) is a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane. 1. A method for producing (R)-1 ,1 ,3-trimethyl-4-aminoindane , comprising the following steps (A) , (B) , and (C):(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;(B): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (C) to obtain 1,1,3-trimethyl-4-aminoindane; and(C): a step of optically resolving the 1,1,3-trimethyl-4-aminoindane obtained in the step (B) to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane.2. The production method according to claim 1 , wherein the steps (B) and (C) are repeated.3. The production method according to claim 1 , wherein the step (C) is a step of optically resolving the 1 claim 1 ,1 claim 1 ,3-trimethyl-4-aminoindane obtained in the step (B) and the 1 claim 1 ,1 claim 1 ,3-trimethyl-4-aminoindane obtained in a step other than the step (B) to obtain (R)-1 claim 1 ,1 claim 1 ,3-trimethyl-4-aminoindane.4. The production method according to claim 1 , comprising the following steps (A) claim 1 , (B′) claim 1 , (D) claim 1 , and (E):(A): a step of optically resolving 1,1,3-trimethyl-4-aminoindane to obtain (R)-1,1,3-trimethyl-4-aminoindane and (S)-1,1,3-trimethyl-4-aminoindane;(B′): a step of racemizing the (S)-1,1,3-trimethyl-4-aminoindane obtained in the step (A) or (E) to obtain 1,1,3-trimethyl ...

PROCESSES FOR MAKING, AND METHODS OF USING, GLYCOPYRRONIUM COMPOUNDS

Provided herein are processes for making and methods of using salts of glycopyrronium, including solid forms and forms suitable for use as topicals. Disclosed here are processes for making salts of glycopyrronium, also processes for making compositions comprising salts of glycopyrronium, and methods of treating hyperhidrosis with salts of glycopyrronium as well as with compositions comprising salts of glycopyrronium such as, but not limited to, topical compositions. Disclosed herein are methods of treating hyperhidrosis including administering salts of glycopyrronium to subjects in need thereof. 2. The process of claim 1 , further comprising:step (3) isolating a stereomerically pure stereoisomer of a compound of Formula (I).3. The process of claim 2 , wherein isolating a stereomerically pure stereoisomer of a compound of Formula (I) is by column chromatography or by simulated moving bed (SMB) separation.4. (canceled)5. (canceled)6. The process of claim 1 , wherein Ris alkyl.7. The process of claim 6 , wherein Ris methyl claim 6 , ethyl claim 6 , n-propyl claim 6 , propyl claim 6 , n-butyl claim 6 , t-butyl claim 6 , i-butyl claim 6 , n-pentyl claim 6 , or i-pentyl.8. The process of claim 7 , wherein Ris methyl or ethyl.9. (canceled)10. (canceled)11. The process of claim 1 , wherein Ris alkyl.12. The process of claim 11 , wherein Ris methyl claim 11 , ethyl claim 11 , n-propyl claim 11 , propyl claim 11 , n-butyl claim 11 , t-butyl claim 11 , i-butyl claim 11 , n-pentyl claim 11 , or i-pentyl.13. The process of claim 12 , wherein Ris methyl or ethyl.14. (canceled)15. (canceled)16. The process of claim 1 , wherein Ris alkyl substituted with alkoxycarbonyl.17. (canceled)18. The process of claim 16 , wherein R—CHC(O)OCHCH.19. (canceled)20. (canceled)21. The process of claim 18 , wherein Ris methyl.22. (canceled)23. The process of claim 1 , wherein in step (1) claim 1 , compounds of Formula (Ia) and Formula (Ib) are stereomerically pure.27. (canceled)28. (canceled)33. ( ...

PROCESSES FOR THE RESOLUTION OF BENZODIAZEPIN-2-ONE AND BENZOAZEPIN-2-ONE DERIVATIVES

The present invention relates to processes and intermediates useful in the preparation of biologically active molecules, especially in the synthesis of Respiratory Syncytial Virus (RSV) inhibitors. The present invention also relates to processes and intermediates for the preparation of compounds of Formula (I-0) and Formula (I): 3. The process of claim 1 , wherein X is N.4. The process of claim 1 , wherein X is CH.5. The process of claim 1 , wherein step (a) is carried out in a solvent selected from acetonitrile claim 1 , methanol claim 1 , tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , ethyl acetate claim 1 , 1 claim 1 ,2-dimethoxyethane claim 1 , dichloromethane claim 1 , 1 claim 1 ,4-dioxane claim 1 , toluene claim 1 , anisole claim 1 , ethanol claim 1 , acetone claim 1 , N claim 1 ,N-dimethylformamide claim 1 , N claim 1 ,N-dimethylacetamide claim 1 , pyridine and isopropyl acetate or a combination of two or more thereof.6. The process of claim 5 , wherein step (a) is carried out in a solvent selected from tetrahydrofuran and 1 claim 5 ,4-dioxane.7. The process of claim 1 , wherein in step (b) claim 1 , the base is sodium hydroxide claim 1 , potassium carbonate claim 1 , ammonium hydroxide claim 1 , potassium phosphate tribasic or sodium carbonate.8. The process of claim 7 , wherein the base is 1 N sodium hydroxide claim 7 , 5 wt % potassium carbonate claim 7 , 28-30% ammonium hydroxide claim 7 , 10 wt % potassium phosphate tribasic or 5 wt % sodium carbonate.9. The process of claim 1 , wherein in step (a) the compound of Formula (I′) is in a mixture with its enantiomer.10. The process of claim 9 , wherein the mixture is a racemic mixture.13. The process of claim 11 , wherein X is N.14. The process of claim 10 , wherein X is CH.15. The process of claim 11 , wherein step (a) is carried out in a solvent selected from acetonitrile claim 11 , methanol claim 11 , tetrahydrofuran claim 11 , 2-methyltetrahydrofuran claim 11 , ethyl acetate claim 11 , 1 ...

PROCESSES FOR THE RESOLUTION OF BENZODIAZEPIN-2-ONE AND BENZOAZEPIN-2-ONE DERIVATIVES

The present invention relates to processes and intermediates useful in the preparation of biologically active molecules, especially in the synthesis of Respiratory Syncytial Virus (RSV) inhibitors. The present invention also relates to processes and intermediates for the preparation of compounds of Formula (I-0) and Formula (I): 3. The process of claim 1 , wherein X is N.4. The process of claim 1 , wherein X is CH.5. The process of claim 1 , wherein step (a) is carried out in a solvent selected from acetonitrile claim 1 , methanol claim 1 , tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , ethyl acetate claim 1 , 1 claim 1 ,2-dimethoxyethane claim 1 , dichloromethane claim 1 , 1 claim 1 ,4-dioxane claim 1 , toluene claim 1 , anisole claim 1 , ethanol claim 1 , acetone claim 1 , N claim 1 ,N-dimethylformamide claim 1 , N claim 1 ,N-dimethylacetamide claim 1 , pyridine and isopropyl acetate or a combination of two or more thereof.6. The process of claim 5 , wherein step (a) is carried out in a solvent selected from tetrahydrofuran and 1 claim 5 ,4-dioxane.7. The process of claim 1 , wherein in step (b) claim 1 , the base is sodium hydroxide claim 1 , potassium carbonate claim 1 , ammonium hydroxide claim 1 , potassium phosphate tribasic or sodium carbonate.8. The process of claim 7 , wherein the base is 1N sodium hydroxide claim 7 , 5 wt % potassium carbonate claim 7 , 28-30% ammonium hydroxide claim 7 , 10 wt % potassium phosphate tribasic or 5 wt % sodium carbonate.9. The process of claim 1 , wherein in step (a) the compound of Formula (I′) is in a mixture with its enantiomer.10. The process of claim 9 , wherein the mixture is a racemic mixture.13. The process of claim 11 , wherein X is N.14. The process of claim 11 , wherein X is CH.15. The process of claim 11 , wherein step (a) is carried out in a solvent selected from acetonitrile claim 11 , methanol claim 11 , tetrahydrofuran claim 11 , 2-methyltetrahydrofuran claim 11 , ethyl acetate claim 11 , 1 ...

STEREOCHEMICALLY DEFINED POLYPROPIONATES AND METHODS FOR MAKING AND USING THE SAME

The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries. 23-. (canceled)7. (canceled)931-. (canceled)35. A process for preparing the compound of claim 32 , comprising the steps of:{'claim-ref': {'@idref': 'CLM-00032', 'claim 32'}, 'treating a compound of Formula 1 with an oxidizing agent to form the compound of .'}3637-. (canceled)39. (canceled)4143-. (canceled)4656-. (canceled) This application is a divisional of and claims priority to pending U.S. Utility patent application Ser. No. 15/501,658, which was the U.S. national phase under 35 U.S.C. § 371 of PCT International Patent Application Serial No. PCT/US2015/043535, filed on Aug. 4, 2015, which claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/032,757, filed Aug. 4, 2014, the disclosure of which is hereby incorporated by reference herein in its entirety.The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries.Biologically active natural products have played a key role in the elucidation of cellular processes and biological mechanisms, and have been fruitful sources of therapeutic agents for many decades. Nearly half of the new chemical entities introduced in drug discovery between 1981 and 2002 were natural products or semi-synthetic analogs of natural products. (Vasilevich, N. I., et al., 2012, 55, 7003-7009.) Polypropionate tetrads and pentads comprise a core structural element of many biologically active natural products.The present invention provides stereochemically defined polypropionates, including stereochemically defined pentads and tetrads, and methods for preparing and using the same. ...

SYNTHESIS OF PEPTOID-BASED SMALL MOLECULAR GELATORS FROM MULTIPLE COMPONENT REACTIONS

Described herein are the one-pot synthesis and characterization of a library of low molecular weight peptoid compounds that are able to form gels at room temperature. The compounds are synthesized from biologically-based starting materials, are biocompatible, and are resistant to degradation by proteases and peptidases. The compounds and gels synthesized therefrom can be used in such applications as tissue engineering, drug delivery, separation of biomolecules, and stimulus-responsive advanced materials 2. The compound of claim 1 , wherein Ris an alkyl group claim 1 , an aryl group claim 1 , an alkynyl group claim 1 , or a substituted aryl group.4. The compound of claim 1 , wherein Ris an unsubstituted or substituted phenyl group.5. The compound of claim 4 , wherein the phenyl group is substituted with a bromo group or a nitro group.6. The compound of claim 1 , wherein Ris a butynyl group.8. The compound of claim 7 , wherein Ris methyl claim 7 , Ris phenyl claim 7 , and n is 2.9. The compound of claim 1 , wherein Ris a cycloalkyl group or an alkyl ester of a carboxylic acid.10. The compound of claim 1 , wherein Ris a cyclohexyl group.11. The compound of claim 1 , wherein Ris an ethyl aceto group.12. The compound of claim 1 , wherein Rand Rare hydrogen.13. The compound of claim 1 , wherein Ris hydrogen and Ris a substituted or unsubstituted aryl group.14. The compound of claim 1 , wherein Ris an aryl group claim 1 , a substituted aryl group claim 1 , an alkyl group claim 1 , an amino sugar claim 1 , or a protected amino sugar.15. The compound of claim 1 , wherein Ris an α-methylbenzyl group or an unsubstituted or substituted benzyl group.16. The compound of claim 15 , wherein the benzyl group is substituted with a methoxy group.17. The compound of claim 1 , wherein Ris glucosamine or a protected glucosamine.18. The compound of claim 1 , wherein the compound is(a) N-benzyl-N-(2-(cyclohexylamino)-2-oxoethyl)pent-4-ynamide.(b) N-benzyl-4-bromo-N-(2-(cyclohexylamino)-2- ...

COFORMER SALTS OF (2S,3S)-METHYL 7-FLUORO-2-(4-FLUOROPHENYL)-3-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-4-OXO-1,2,3,4-TETRAHYDROQUINOLINE-5-CARBOXYLATE AND METHODS OF PREPARING THEM

Described herein are coformer salts of (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate optionally as a solvate and additionally optionally as a hydrate, including crystalline forms, and methods of preparing the (2S,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1, 2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate optionally as a coformer salts. 1: A coformer salt of (2S ,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1 ,2 ,4-triazol-5-yl)-4-oxo-1 ,2 ,3 ,4-tetrahydroquinoline-5-carboxylate optionally as a solvate and additionally optionally as a hydrate thereof.2: The coformer salt of claim 1 , wherein the coformer salt is in a substantially pure crystalline form.3: The coformer salt of claim 1 , wherein the coformer salt is a [(1S)-endo]-(+)-3-bromo-10-camphor sulfonic acid salt of (2S claim 1 ,3S)-methyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)-4-oxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinoline-5-carboxylate.4: The coformer salt of claim 1 , wherein the coformer salt is a crystalline form exhibiting at least one of:{'sup': '13', 'a solid state C NMR spectrum with peaks at 210.3, 25.3, 21.8, 20.8, 19.5, and 18.5 ppm±0.2 ppm;'}a differential scanning calorimetry thermogram having a broad endotherm between 25° C. and 90° C. and an endotherm with a maximum between about 135° C. and 147° C.;a thermogravimetric analysis thermogram indicative of a solvated material; ora X-ray powder diffraction pattern comprising peaks at 2θ angle degrees±0.2 2θ angle degrees of 6.7, 9.7, 18.5, 19.5, and 22.5: The coformer salt of claim 1 , wherein the coformer salt is in a crystalline form exhibiting at least one of:a solid state 13C NMR spectrum with peaks at 210.3, 25.3, 21.8, 20.8, 19.5, and 18.5 ppm±0.2 ppm; ora X-ray powder diffraction pattern comprising peaks at 2θ angle degrees±0.2 2θ angle degrees of 6.7, 9.7, 18.5, 19.5, ...

Method for chiral resolution and device therefor

The present invention relates to method for chiral resolution of chiral species contained in a liquid placed in a cell formed by an inner wall and an outer wall surrounding the inner wall over at least a portion of the inner wall, each of the outer and inner walls being a solid of revolution about a longitudinal axis, the outer and inner walls being coaxial to one another, the method comprising: rotating the outer wall in one direction of rotation with respect to the inner wall for generating a Taylor-Couette flow within the liquid; collecting at least one of the chiral species. The present invention also relates to a device therefor.

METHOD FOR PRODUCING PYRROLE DERIVATIVE, AND INTERMEDIATE THEREOF

The present invention provides a method for producing an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, and an intermediate thereof. A method for producing an atropisomer of a pyrrole derivative using a compound represented by (B) [wherein Rrepresents a C1-C4 alkyl group, and Rrepresents a 2-hydroxyethyl group or a carboxymethyl group] as a production intermediate. 5. The method according to claim 3 , wherein the enzyme is a lipase.6. The method according to claim 3 , wherein the enzyme is an immobilized lipase.7. The method according to claim 3 , wherein the solvent is an organic solvent.10. The method according to claim 8 , wherein the optically active amine is (R)-(+)-1-(1-naphthyl)ethylamine.12. A method for producing ethyl (S)-1-(2hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate claim 8 , comprising the following steps of:(i) obtaining an optically active amine salt of (S)-2-[4-ethoxycarbonyl-3-methyl-2-[2-(trifluoromethyl)phenyl]-1H-pyrrol-1-yl]acetic acid by resolving (RS)-2-[4-ethoxycarbonyl-3-methyl-2-[2-(trifluoromethyl)phenyl]-1H-pyrrol-1-yl]acetic acid in a solvent using an optically active amine;(ii) removing the optically active amine under an acidic condition; and thereafter(iii) performing reduction using a reducing agent.13. The method according to claim 11 , wherein the reducing agent is sodium borohydride.14. The method according to claim 11 , wherein the optically active amine is quinine claim 11 , cinchonine claim 11 , or (R)-1-(1-naphthyl)ethylamine.15. The method according to claim 11 , wherein the optically active amine is cinchonine.16. The method according to claim 11 , wherein the solvent is an organic solvent.18. The production method according to claim 17 , wherein the reagent is a Grignard reagent.20. The method according to claim 4 , wherein the enzyme is a lipase.21. The method according to claim 4 , wherein the enzyme is an immobilized lipase.22. The ...

Synthetic Route to 2'-Deoxy-2',2'-Difluorotetrahydrouridines

The present invention relates to methods and intermediates for synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine compounds. 2. The method of claim 1 , wherein the catalyst is a Bronsted-Lowry base.3. The method of claim 1 , wherein the catalyst is about 1 mol % to about 20 mol % 1 claim 1 ,8-diazabicyclo(5.4.0)undec-7-ene (DBU).4. The method of claim 1 , wherein the catalyst is about 5 mol % to about 10 mol % DBU.5. The method of claim 4 , wherein the catalyst is about 5 mol % DBU.6. The method of claim 1 , wherein the catalyst is acetic acid claim 1 , trifluoroacetic acid claim 1 , diisopropylethylamine claim 1 , or ammonium hydroxide.7. The method of claim 1 , wherein the solution comprises acetonitrile.8. The method of claim 1 , wherein the solution comprises acetone claim 1 , tetrahydrofuran claim 1 , DMSO claim 1 , or methanol.10. The method of claim 9 , wherein the catalyst is about 1 mol % to about 20 mol % DBU11. The method of claim 10 , wherein the catalyst is about 5 mol % to about 10 mol % DBU.12. The method of claim 11 , wherein the catalyst is about 5 mol % DBU.13. The method of claim 9 , wherein the catalyst is acetic acid claim 9 , trifluoroacetic acid claim 9 , diisopropylethylamine claim 9 , or ammonium hydroxide.14. The method of claim 9 , wherein the final product is recrystallized or slurrified.15. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetonitrile.16. The method of claim 9 , wherein step (d) is carried out in the presence of a solution comprising acetone or tetrahydrofuran.17. The method of claim 9 , wherein step (b) is carried out in the presence of CeCl.18. The method of claim 9 , further comprising a step of reducing the particle size of compound 1.19. The method of claim 18 , wherein the particle size is reduced to about 50 μm or less.24. The compound of claim 20 , wherein Ris H or absent.30. Compound 1 of claim 29 , having a purity of at least about 95%. This application claims ...

METHOD FOR PRODUCING PYRROLE DERIVATIVE, AND INTERMEDIATE THEREOF

The present invention provides a method for producing an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, and an intermediate thereof. A method for producing an atropisomer of a pyrrole derivative using a compound represented by (B) [wherein Rrepresents a C1-C4 alkyl group, and Rrepresents a 2-hydroxyethyl group or a carboxymethyl group] as a production intermediate. 2. A compound according to claim 1 , wherein Ris an ethyl group.3. A compound according to claim 1 , wherein Ris a 2-hydroxyethyl group.4. A compound according to claim 1 , wherein Ris a carboxymethyl group. This application is a division of U.S. application Ser. No. 15/699,954, filed Sep. 8, 2017, which is a division of U.S. application Ser. No. 15/043,260, filed Feb. 12, 2016, which is a continuation of International Application No. PCT/JP2014/072332, filed Aug. 26, 2014, which claims priority from Japanese Application No. 2013-175172, filed Aug. 27, 2013. Each application is incorporated herein by reference in its entirety.The present invention relates to a method for producing an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, and a production intermediate thereof.A mineralocorticoid receptor (MR) (aldosterone receptor) is known to play an important role in regulating electrolyte balance and blood pressure in the body, and MR antagonists having a steroidal structure such as spironolactone and eplerenone are known to be useful for the treatment of hypertension and heart failure.1-(2-Hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)-phenyl]-5-[2-(trifluoromethyl) phenyl]-1H-pyrrole-3-carboxamide, which is a pyrrole derivative, is disclosed in PTL 1. Further, an atropisomer thereof is disclosed in PTL 2 and is known to be useful for the treatment of hypertension, diabetic nephropathy, and the like.PTL 1: WO 2006/012642 (US Patent Application No. US 2008-0234270)PTL 2: WO 2008/126831 (US Patent ...

Nahlsgen optical resolution method

Provided is a method for separating the four optical isomers of Nahlsgen. The method according to the present invention for producing a mixture of a D-2-amino-4-[(Rp)-(3-carboxymethylphenoxy)(methoxy)phosphoryl]butanoic acid hydrate and an L-2-amino-4-[(Sp)-(3-carboxymethylphenoxy)(methoxy)phosphoryl]butanoic acid hydrate includes subjecting a mixture of the four optical isomers, represented by Formula (1′), to fractional crystallization from water or from a solvent mixture of water and a water-soluble organic solvent, to precipitate a mixture of a compound represented by Formula (1-1′-1) and a compound represented by Formula (1-4′-1), where Formulae (1′), (1-1′-1), and (1-4′-1) are expressed as follows:

TAU IMAGING PROBE

An object of the present invention is to provide a compound represented by formula (I) which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or undetected toxicity. 4. A pharmaceutical composition comprising the compound according to or a pharmaceutically acceptable salt or solvate thereof claim 1 , and a pharmaceutically acceptable carrier.5. A pharmaceutical composition for the treatment and/or prevention of conformational disease 1 , comprising the compound according to claim or a pharmaceutically acceptable salt or solvate thereof 1 , and a pharmaceutically acceptable carrier.6. The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is an injection.7. The compound according to claim 1 , wherein the compound is labeled claim 1 , or a pharmaceutically acceptable salt or solvate thereof.8. The compound according to claim 7 , wherein the label is any one kind of a radioactive nuclide or a positron emitting nuclide.9. The compound according to claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein the radioactive nuclide is a γ-ray emitting nuclide.10. The compound according to claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein the positron emitting nuclide is selected from the group consisting of C claim 8 , N claim 8 , O claim 8 , F claim 8 , Cl claim 8 , Br claim 8 , Ti claim 8 , V claim 8 , Cu claim 8 , Cu claim 8 , Cu claim 8 , Cu claim 8 , Ga claim 8 , Zr claim 8 , Tc and I.11. The compound according to claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein the positron emitting nuclide is F.12. The compound according to claim 1 , wherein said halogen atom is an F atom(s) and said compound is/are labeled with F.13. The compound according to claim 12 , wherein said halogen atom is an F atom(s) and said compound is/are ...

STEREOCHEMICALLY DEFINED POLYPROPIONATES AND METHODS FOR MAKING AND USING THE SAME

The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries. 23-. (canceled)7. (canceled)910-. (canceled)1214-. (canceled)1619-. (canceled)20. The process of claim 15 , wherein the isolated first diastereomeric salt is treated with a base to form a first enantiomeric compound of Formula 1.2223-. (canceled)24. The process of claim 15 , further comprising the steps of:acidifying the second diastereomeric salt to form a free phthalate;reacting the free phthalate with a second chiral amine to reform the second diastereomeric salt in a solution;precipitating the second diastereomeric salt from the solution to form an isolated second diastereomeric salt; andforming a second enantiomeric compound of Formula 1 from the isolated second diastereomeric salt.2529-. (canceled)31. (canceled)35. A process for preparing compound of claim 32 , comprising the steps of:{'claim-ref': {'@idref': 'CLM-00032', 'claim 32'}, 'treating a compound of Formula 1 with an oxidizing agent to form the compound of .'}3637-. (canceled)39. (canceled)4143-. (canceled)4656-. (canceled) This application claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/032,757, filed Aug. 4, 2014, the disclosure of which is hereby incorporated by reference herein in its entirety.The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries.Biologically active natural products have played a key role in the elucidation of cellular processes and biological mechanisms, and have been fruitful sources of therapeutic agents for many decades. Nearly half of the new chemical entities introduced in drug discovery between ...

PROCESS FOR PREPARING (CYCLOPENTYL[d]PYRIMIDIN-4-YL)PIPERAZINE COMPOUNDS

The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes. 3. The process of claim 2 , wherein Y is bromo.4. The process of or claim 2 , wherein Lv is selected from hydrogen and a halogen claim 2 , and Ris selected from acetyl claim 2 , trifluoroacetyl claim 2 , phthalimidyl claim 2 , benzyl claim 2 , triphenylmethyl claim 2 , benzylidenyl claim 2 , p-toluenesulfonyl claim 2 , p-methoxybenzyl claim 2 , tertbutyloxycarbonyl claim 2 , 9-fluorenylmethyloxycarbonyl and carbobenzyloxy.5. The process of any one of - claim 2 , wherein the compound of Formula IV claim 2 , or salt thereof claim 2 , is contacted with from about 1 molar equivalent to about 1.5 molar equivalents of the piperazine compound.6. The process of any one of - claim 2 , wherein the compound of Formula IV claim 2 , or salt thereof claim 2 , is contacted with the piperazine compound at room temperature.8. The process of claim 7 , wherein each X is chloro.9. The process of claim 7 , wherein each X is hydroxyl.10. The process of any one of - claim 7 , wherein the brominating agent is selected from bromine claim 7 , bromotrimethylsilane claim 7 , phosphorus oxybromide claim 7 , N-bromosuccinimide claim 7 , and phosphorus tribromide.11. The process of any one of - claim 7 , wherein the compound of Formula V claim 7 , or salt thereof claim 7 , is contacted with from about 2 molar equivalents to about 7 molar equivalents of the brominating agent.12. The ...

METHOD FOR THE SEPARATION OF ENANTIOMERIC MIXTURES FROM METAL COMPLEXES

The present invention relates to processes for separating mixtures containing enantiomers of metal complexes with aromatic and/or heteroaromatic ligands, to metal complexes and to electronic devices, especially organic electroluminescent devices, comprising these metal complexes. 118-. (canceled)19. A process for separating mixtures containing enantiomers of metal complexes with aromatic and/or heteroaromatic ligands , comprising the steps of:A) providing a mixture of reactive metal complexes, wherein the mixture comprises at least two enantiomers of the reactive metal complexes;B) reacting the mixture provided in step A) with an optically active boron compound to obtain a diastereomer mixture; andC) separating the diastereomer mixture obtained in step B).20. The process of claim 19 , wherein a mixture of metal complexes is used claim 19 , wherein the reactive metal complexes are reactive metal complexes of formula (1):{'br': None, 'sub': n', 'm, 'Ir(L)(L′)\u2003\u2003(1)'} L is the same or different in each instance and is a bidentate ligand;', 'L′ is the same or different in each instance and is a ligand;', 'n is 1, 2, or 3; and', 'm is 0, 1, 2, 3, or 4;, 'wherein'}and wherein two or more ligands L are optionally joined together or L is optionally joined to L′ via a single bond or a bivalent or trivalent bridge so as to define a tridentate, tetradentate, pentadentate, or hexadentate ligand system.22. The process of claim 19 , wherein the metal complex has one claim 19 , two claim 19 , or three bidentate ligands claim 19 , wherein the bidentate ligands are the same or different in each instance and have one carbon atom and one nitrogen atom or two carbon atoms or two nitrogen atoms or two oxygen atoms or one oxygen atom and one nitrogen atom as coordinating atoms.29. A metal complex obtained by the process of .30. A metal complex of formula (1b){'br': None, 'sub': n', 'm, 'Ir(L)(L′)\u2003\u2003(1b)'} L is the same or different in each instance and is a bidentate ...

ENANTIOSELECTIVE DESTRUCTION OF CHIRAL MOLECULES

Methods and devices are disclosed for selective photo-destruction of one chiral enantiomer of a compound using nanostructures by enhancing differential absorption of circularly polarized light by the one chiral enantiomer. Methods and devices are disclosed for selective enrichment of one chiral enantiomer of a compound using nanostructures by enhancing differential absorption of circularly polarized light by the one chiral enantiomer. The nanostructures support optical frequency electric resonances and optical frequency magnetic resonances. 1. A method for selective photo-destruction of one chiral enantiomer of a compound , the method comprising:providing a solution comprising two chiral enantiomers of the compound;adding a nanostructure to the solution;irradiating the solution with a circularly polarized light; andexposing the solution to a local electric field and a local magnetic field, such that the circularly polarized light is differentially absorbed by the one chiral enantiomer, thereby achieving the selective photo-destruction of the one chiral enantiomer of the compound.2. The method of claim 1 , wherein the nanostructure supports optical frequency electric resonances and optical frequency magnetic resonances.3. The method of claim 2 , wherein the nanostructure is excited with the circularly polarized light claim 2 , thereby causing interference between the optical frequency electric resonances and optical frequency magnetic resonances.4. The method of claims 3 , wherein an amount of differential absorption of the circularly polarized light by the one chiral enantiomer and a rate of differential absorption of the circularly polarized light by the one chiral enantiomer are enhanced.5. The method of claim 4 , wherein the amount of differential absorption of the circularly polarized light by the one chiral enantiomer is enhanced about 17-fold to about 510-fold.6. The method of claim 4 , wherein the rate of differential absorption of the circularly polarized ...

Antifungal compound process

The present invention relates to a process for preparing a compound of 5 or 5*, or a mixture thereof, and/or a compound of 14 or 14*, or a mixture thereof, that is useful as an antifungal agent. In particular, the invention seeks to provide new methodology for preparing compounds 7, 7* and 11, 11* and substituted derivatives thereof.

A CRYSTALLINE METAL ORGANIC FRAMEWORK

The present invention relates to a crystalline metal organic framework which comprises repeating units of formula (RR)-(IA) or (SS)-(IA) or (RS)-(IA) or (SR)-(IA); or alternatively of formula (RR)-(IB) or (SS)-(IB) or (RS)-(IB) or (SR)-(IB) and a composition containing it. It also relates to processes for their preparation and their uses as a separation agent and as a catalyst. 3. The metal organic framework according to claim 1 , wherein M is a divalent metal selected from the group consisting of Cu claim 1 , Zn claim 1 , V claim 1 , Pd claim 1 , Pt claim 1 , Ni claim 1 , Ru claim 1 , Hg claim 1 , Sn claim 1 , Co claim 1 , Fe claim 1 , Mn claim 1 , Cr claim 1 , Cd claim 1 , Be claim 1 , Mg claim 1 , Ca claim 1 , Ba claim 1 , Zr claim 1 , Gd claim 1 , Eu claim 1 , Tb and mixtures thereof.6. The metal organic framework according to claim 5 , wherein:{'sup': '−10', 'the repeating unit has the formula (SS)-(IB1′) and the metal organic framework has a X-ray diffractogram that comprises characteristic peaks at 6.2, 7.6, 9.8, 10.7, 14.5, 15.2, 17.6, 18.1, 19.2, 19.7, 20.2, 20.6, 22.5, 22.9, 23.7, 24.2, 26.1, 27.2, 28.3, 30.0, 32.6, 33.2, 33.5, 34.1, 35.0 and 37.0±0.2 degrees 2 theta measured in an X-ray diffractometer with Cu Kα radiation (1.5406*10m (Å)); or alternatively'}the repeating unit has the formula (SS)-(IB1′) and the metal organic framework is characterized by having the following crystallographic parameters measured by single X-ray diffraction:Crystal system: cubic;Space group: P4(3)/32;{'sup': '−10', 'claim-text': [{'sup': '−10', 'b=20.172(2)*10m (Å) β=90°,'}, {'sup': '−10', 'c=20.172(2)*10m (Å) γ=90°;'}], 'Unit cell dimensions: a=20.172(2)*10m (Å) α=90°,'}{'sup': −10', '3, 'Volume: 8208(2)*10m(Å); and'}{'sup': '3', 'Density: 1.359 Mg/m.'}7. (canceled)8. The metal organic framework according to claim 5 , wherein{'sup': '2', 'the repeating unit has the formula (SS)-(IA1) and the metal organic framework has a BET surface area from 250 to 1800 m/g; or ...

Method for producing 2-pyridone compound

To provide a method for producing a compound represented by the formula (1) which is a 2-pyridone compound useful as a pharmaceutical or an intermediate for a pharmaceutical, etc. at a high yield. A method for producing a 2-pyridone compound represented by the formula (1), which comprises reacting a 6-benzoyl-2-pyridone compound represented by the formula (3) with a sulfone compound represented by the formula (4):

PROCESS FOR THE PREPARATION OF (1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL)-PHENOL

The present invention relates to a process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol. 2. A process according to claim 1 , wherein R represents methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl claim 1 , tert-butyl claim 1 , n-pentyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , cycloheptyl claim 1 , benzyl claim 1 , phenethyl claim 1 , tetrahydropyranyl claim 1 , —C(═O)—CH claim 1 , —C(═)—CH claim 1 , —C(═O)—CH(CH)or —C(═O)—C(CH).3. A process according to claim 2 , wherein R represents methyl claim 2 , ethyl claim 2 , cyclopropyl claim 2 , cyclobutyl claim 2 , cyclopentyl claim 2 , cyclohexyl claim 2 , benzyl claim 2 , phenethyl claim 2 , tetrahydropyranyl or —C(═O)—CH.4. A process according to claim 3 , wherein R represents methyl claim 3 , benzyl or tetrahydropyranyl.5. A process according to claim 1 , wherein the ethyl magnesium halide used in step (a) is the chloride or bromide.6. A process according to claim 1 , wherein the inert reaction medium is selected from the group consisting of diethyl ether claim 1 , tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , tert-butyl-methylether claim 1 , diisopropylether or any mixture thereof.8. A process according to claim 7 , wherein R represents methyl claim 7 , ethyl claim 7 , n-propyl claim 7 , isopropyl claim 7 , n-butyl claim 7 , isobutyl claim 7 , tert-butyl claim 7 , n-pentyl claim 7 , cyclopropyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , cycloheptyl claim 7 , benzyl claim 7 , phenethyl claim 7 , tetrahydropyranyl claim 7 , —C(═O)—CH claim 7 , —C(═O)—CH claim 7 , —C(═O)—CH(CH)or —C(═O)—C(CH).9. A process according to claim 8 , wherein R represents methyl claim 8 , ethyl claim 8 , cyclopropyl claim 8 , cyclobutyl claim 8 , cyclopentyl claim 8 , cyclohexyl claim 8 , benzyl claim 8 , phenethyl claim 8 , tetrahydropyranyl or —C(═O)—CH.10. A ...

A simple Process for Preparing an Intermediate for Avibactam

A compound of Formula III as the raw material is hydrolyzed in an alkaline condition, then acidized to prepare a compound of Formula IV, and the resulting compound of formula IV and a solid phosgene or diphosgene are concurrently subjected to the urea cyclization and the chloroformylation reaction in the presence of an organic base and a catalyst to obtain a compound of formula V, and then the compound of formula V is amidated to obtain the final product (II). In the present invention, a “one-pot” method is adopted for urea cyclization, chloroformylation, and amidation reaction, and the intermediate products do not need post-treatments such as separation and purification.

CHIRAL RESOLUTION OF AN INTERMEDIATE OF SUVOREXANT AND COCRYSTALS THEREOF

Relating to processes for preparing suvorexant or its pharmaceutically acceptable salts through the formation of a cocrystal of (R)-benzyl 5-methyl-1,4-diazepane-1-carboxylate hydrochloride with (R)-(+)-1,1,2-triphenyl-1,2-ethanediol ((R)-TED). This cocrystal provides the resolution of an intermediate of suvorexant, in particular, of (rac)-benzyl5-methyl-1,4-diazepane-1-carboxy-lateor a hydrochloride salt thereof. It also relates to a new cocrystal useful in such preparation processes. 2. The cocrystal according to claim 1 , which is a crystalline form named Form A claim 1 , and is characterized by having an X-ray diffractogram that comprises characteristic peaks at approximately 5.3 claim 1 , 10.6 claim 1 , and 15.8 degrees 2 theta at a Cu—Kradiation claim 1 , λ=1.5406 Å.3. The cocrystal according to claim 2 , which is characterized by further comprising characteristic peaks in the X-ray powder diffractogram at approximately 9.8 claim 2 , 12.9 claim 2 , and 19.7 degrees 2 theta at a Cu—Kradiation claim 2 , λ=1.5406 Å.4. The cocrystal according to claim 3 , characterized in that the endothermic sharp peak corresponding to the melting point has an onset at about 152° C.6. The resolution process according to claim 3 , further comprising a recrystallization step of the cocrystal obtained in step a) of claim 3 , in a solvent selected from the group consisting of acetonitrile claim 3 , isopropanol claim 3 , ethyl acetate claim 3 , acetone claim 3 , and toluene.7. The resolution process according to claim 5 , wherein the solvent of the preparation step is acetonitrile.8. The resolution process according to claim 5 , wherein the solvent of the recrystallization step is acetonitrile.10. The resolution process according to claim 9 , wherein the dissociation step comprises:(1) slurrying the cocrystal of (R)-benzyl 5-methyl-1,4-diazepane-1-carboxylate hydrochloride with (R)-TED of formula (II), in water between 0° C. and room temperature;(2) separating the (R)-TED from the ...

METHOD FOR PRODUCING D-FORM OR L-FORM AMINO ACID DERIVATIVE HAVING THIOL GROUP

The object of the present invention is to provide a method of efficiently manufacturing an optically active D- and/or L-form amino acid possessing a thiol group in the side chain by a simple method. The present invention provides a method of manufacturing an amino acid derivative possessing a thiol group in the side chain, characterized in manufacturing an intermediate composition comprising D- and L-forms of an amino acid derivative possessing a thiol group at the β-position, reacting a hydrolase selective for D- or L-amino acids, and separating the hydrolyzed D- or L-amino acid derivative, as well as an intermediate thereof. 2. The method according to claim 1 , which is a method of manufacturing a non-natural D- or L-amino acid derivative possessing a protected or non-protected thiol group and substituent Rat the β-position claim 1 , wherein Rrefers to the substituent moiety bound to the β carbon atom among side chain substituents that configure amino acids claim 1 , except when it is a hydrogen atom claim 1 , andsaid step (I) comprises the following step (P) before said reaction (A):{'sup': '1', '(P) manufacturing an amino acid derivative possessing substituent Rand a leaving group L on the β carbon atom, and'}said reaction (A) is carried out simultaneously with a reaction of detaching said leaving group L from the β carbon atom of the amino acid derivative.3. The method according to claim 2 , wherein{'sup': '1', 'substituent Ris an aromatic substituent, and'}said step (P) comprises the following step (P-1):{'sup': '1', '(P-1) introducing a leaving group L at the β carbon atom of an amino acid derivative possessing substituent Ron the β carbon atom.'}4. The method according to claim 2 , whereinsaid step (P) comprises the following step (P-2):{'sup': '1', '(P-2) reacting glycine with an aldehyde compound represented by RCHO.'}5. The method according to claim 1 , whereinsaid step (B) comprises converting the amino group bound to the α carbon atom of said amino acid ...

(R) ENANTIOMERS OF CARBOXAMIDES FOR CONTROLLING OF HARMFUL MICROORGANISMS OR FOR ENHANCING PLANT HEALTH

The present invention relates to (R)-enantiomers of certain carboxamides, to compositions comprising these (R)-enantiomers, to a process for preparing these enantiomers and to the use for controlling of harmful microorganisms and for enhancing plant health in conventionally bred or transgenic plants of the Phaseoleae tribe, in particular conventionally bred or transgenic soybean. 3. An (R)-enantiomer of formula (I) according to capable of being used for controlling harmful microorganisms or enhancing plant health in conventionally bred or transgenic plants of the Phaseoleae tribe.4. An (R)-enantiomer of formula (I) according to wherein the plant is soybean.5. An (R)-enantiomer of formula (I) according to wherein the plant is transgenic soybean.6. An (R)-enantiomer of formula (I) according to capable of being used for controlling harmful microorganisms or enhancing plant health wherein the plant is conventionally bred soybean.7. An (R)-enantiomer of formula (I) according to capable of being used for controlling harmful microorganisms or enhancing plant health wherein the seed of the plants are treated.8. Process for preparing the compound of formula (I) according to claim 1 , comprising separating racemic compounds according to formula (I) by preparative HPLC on a chiral stationary phase.9. Agrochemical composition claim 1 , comprising the compound of formula (I-(R)) according to and one or more extenders or surfactants.10. A soybean seed treated with a composition according to . The present invention relates to (R)-enantiomers of certain carboxamides, to compositions comprising these (R)-enantiomers, to a process for preparing these enantiomers and to the use for controlling of harmful microorganisms and for enhancing plant health in conventionally bred or transgenic plants of the Phaseoleae tribe, in particular conventionally bred or transgenic soybean.whereinThe carboxamides described have one chirality center and, if further centres of chirality are absent, two ...

PROCESS FOR THE PREPARATION OF (1R,2R)-3-(3-DIMETHYLAMINO-1-ETHYL-2-METHYL-PROPYL)-PHENOL

The present invention relates to a process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol. 2. A process according to claim 1 , wherein R represents methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl claim 1 , tert-butyl claim 1 , n-pentyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , cycloheptyl claim 1 , benzyl claim 1 , phenethyl claim 1 , tetrahydropyranyl claim 1 , —C(═O)—CH claim 1 , —C(═O)—CH claim 1 , —C(═O)—CH(CH)or —C(═O)—C(CH).3. A process according to claim 2 , wherein R represents methyl claim 2 , ethyl claim 2 , cyclopropyl claim 2 , cyclobutyl claim 2 , cyclopentyl claim 2 , cyclohexyl claim 2 , benzyl claim 2 , phenethyl claim 2 , tetrahydropyranyl or —C(═O)—CH.4. A process according to claim 3 , wherein R represents methyl claim 3 , benzyl or tetrahydropyranyl.5. A process according to claim 1 , wherein the ethyl magnesium halide used in step (a) is the chloride or bromide.6. A process according to claim 1 , wherein the inert reaction medium is selected from the group consisting of diethyl ether claim 1 , tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , tert-butyl-methylether claim 1 , diisopropylether or any mixture thereof.8. A process according to claim 7 , wherein R represents methyl claim 7 , ethyl claim 7 , n-propyl claim 7 , isopropyl claim 7 , n-butyl claim 7 , isobutyl claim 7 , tert-butyl claim 7 , n-pentyl claim 7 , cyclopropyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , cycloheptyl claim 7 , benzyl claim 7 , phenethyl claim 7 , tetrahydropyranyl claim 7 , —C(═O)—CH claim 7 , —C(═O)—CH claim 7 , —C(═O)—CH(CH)or —C(═O)—C(CH).9. A process according to claim 8 , wherein R represents methyl claim 8 , ethyl claim 8 , cyclopropyl claim 8 , cyclobutyl claim 8 , cyclopentyl claim 8 , cyclohexyl claim 8 , benzyl claim 8 , phenethyl claim 8 , tetrahydropyranyl or —C(═O)—CH.10. A ...

POLYMORPHIC AND AMORPHOUS FORMS OF (R)-2-HYDROXY-2-METHYL-4-(2,4,5-TRIMETHYL-3,6-DIOXOCYCLOHEXA-1,4-DIENYL)BUTANAMIDE

Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms. 1. A polymorph of an anhydrate , a hydrate , or a solvate of (R)-2-hydroxy-2-methyl-4-(2 ,4 ,5-trimethyl-3 ,6-dioxocyclohexa-1 ,4-dienyl)butanamide , wherein the polymorph is selected from the group consisting of Form I (anhydrate) , Form V (solvate) , Form III (hydrate) , Form II (anhydrate) , Form IV (solvate) , or Form VI (solvate); wherein a powder X-ray diffraction pattern for polymorph Form I comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2:12.06 , 17.03 , and 17.26; wherein a powder X-ray diffraction pattern for polymorph Form V comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2:9.61 , 11.49 , and 15.45; wherein a powder X-ray diffraction pattern for polymorph Form III comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2:14.02 , 15.23 , and 21.10; wherein a powder X-ray diffraction pattern for polymorph Form II comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2:9.63 , 11.33 , and 19.33; wherein a powder X-ray diffraction pattern for polymorph Form IV comprises characteristic peaks at least at the following angular positions , wherein the angular positions may vary by ±0.2:4.31 , 12.97 , and 13.20; and wherein a powder X-ray diffraction pattern for polymorph Form VI comprises characteristic peaks at least at the ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , or naphthyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.8. The compound of or the pharmaceutically acceptable salt thereof claim 7 , wherein Ris in each instance independently selected from —CH claim 7 , —F claim 7 , —Cl claim 7 , —Br claim 7 , —CN claim 7 , —CF claim 7 , —OCH claim 7 , —OCHF claim 7 , —OCHCH claim 7 , —C(═O)OCH claim 7 , —C(═O)CH claim 7 , or —N(CH).10. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.11. The compound of or the pharmaceutically acceptable salt thereof claim 10 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.12. The compound of or the pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from a group of formula —(CRR)-Q claim 1 , a group of formula —NH—(CRR)-Q claim 1 , a group of formula —(CRR)—C(═O)-Q claim 1 , a group of formula —(CRR)—(CRR)-Q claim 1 , a group of formula —(CR═CR)-Q claim 1 , or a group of formula -(heterocyclyl)-Q claim 1 , wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of which 1 claim 1 , 2 claim 1 , or 3 are heteroatoms selected from N claim 1 , O claim 1 , or S and is unsubstituted ...

POLYELECTROLYTE COMPLEXES

The present invention relates to aqueous compositions of associative polyelectrolyte complexes (PECs), optionally containing surfactants, biocidal agents and/or oxidants, which can provide a cleaning benefit and surface protection to treated articles including reduced soiling tendency, reduced cleaning effort and improved soil repellency, as well as providing bacteriostatic properties to treated surfaces that thereby gain resistance to water, environmental exposure and microbial challenge. Treatment means and compositions are provided that employ associative polyelectrolyte complexes formed by combining a water soluble cationic first polyelectrolyte with a water soluble second polyelectrolyte bearing groups of opposite charge to the first polyelectrolyte under suitable mixing conditions and at least one oxidant selected from the group: alkaline metal salts and/or alkaline earth metal salts of hypochlorous acid, hypochlorous acid, solubilized chlorine, any source of free chlorine, acidic sodium chlorite, active chlorine generating compound and any combinations or mixtures thereof. Also provided are means to form stable associative polyelectrolyte complexes with at least one oxidant in aqueous solutions having R values from about 0.10 to 20. 1. A treatment composition comprising:(i) water;(ii) an anionic surfactant;(iii) an oxidant;(iv) at least one water-soluble associative polyelectrolyte complex comprising a water soluble cationic first polyelectrolyte; and a water soluble second polyelectrolyte bearing groups of opposite charge to said first polyelectrolyte; wherein the resulting water-soluble associative polyelectrolyte complex is non-precipitating in the treatment composition, wherein R, the molar ratio of charged groups present on said first polyelectrolyte to oppositely charged groups present on said second polyelectrolyte is from about 0.10 to 20;(v) wherein said cationic first polyelectrolyte and said second polyelectrolyte each comprise at least one of ...

TRIAZOLE AGONISTS OF THE APJ RECEPTOR

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: 2. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 Rsubstituents.6. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris —H.7. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris a phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , isoxazolyl claim 1 , indolyl claim 1 , naphthyl claim 1 , or pyridinyl any of which may be unsubstituted or substituted with 1 claim 1 , 2 claim 1 , or 3 Rsubstituents.8. The compound of or the pharmaceutically acceptable salt thereof claim 7 , the stereoisomer of any of the foregoing claim 7 , or the mixture thereof claim 7 , wherein Ris in each instance independently selected from —CH claim 7 , —F claim 7 , —Cl claim 7 , —Br claim 7 , —CN claim 7 , —CF claim 7 , —OCH claim 7 , —OCHF claim 7 , —OCHCH claim 7 , —C(═O)OCH claim 7 , —C(═O)CH claim 7 , or —N(CH).10. The compound of or the pharmaceutically acceptable salt thereof claim 1 , the stereoisomer of any of the foregoing claim 1 , or the mixture thereof claim 1 , wherein Ris a phenyl substituted with 1 or 2 Rsubstituents.11. The compound of or the pharmaceutically acceptable salt thereof claim 10 , the stereoisomer of any of the foregoing claim 10 , or the mixture thereof claim 10 , wherein the 1 or 2 Rsubstituents are —O—(C-Calkyl) groups.12. The compound of or the ...

Kinetic resolution of racemic hydroxy ester via asymmetric catalytic hydrogenation and application thereof

The present invention relates to kinetic resolution of racemic δ-hydroxyl ester via asymmetric catalytic hydrogenation and an application thereof. In the presence of chiral spiro pyridyl phosphine ligand Iridium catalyst and base, racemic δ-hydroxyl esters were subjected to asymmetric catalytic hydrogenation to obtain extent optical purity chiral δ-hydroxyl esters and corresponding 1,5-diols. The method is a new, efficient, highly selective, economical, desirably operable and environmentally friendly method suitable for industrial production. An optically active chiral δ-hydroxyl ester and 1,5-diols can be obtained at very high enantioselectivity and yield with relatively low usage of catalyst. The chiral δ-hydroxyl ester and 1,5-diols obtained by using the method can be used as a critical raw material for asymmetric synthesis of chiral drugs (R)-lisofylline and natural drugs (+)-civet, (−)-indolizidine 167B and (−)-coniine. 3. The kinetic resolution method of racemic δ-hydroxyl esters via asymmetric catalytic hydrogenation according to claim 1 , wherein claim 1 , Ris C˜Calkyl claim 1 , phenyl claim 1 , cyclopentyl tert-butyloxyl methyl.4. The kinetic resolution method of racemic -hydroxyl esters via asymmetric catalytic. hydrogenation according to or claim 1 , wherein claim 1 , the said racemic δ-hydroxyl esters also included δ-hydroxyl lactone esters.8. The kinetic resolution method of racemic δ-hydroxyl esters via asymmetric catalytic hydrogenation according to claim 2 , wherein claim 2 , in the presence of organic solvent claim 2 , were added δ-hydroxyl esters claim 2 , catalysts claim 2 , base; the reaction mixture was stirred for 0.5-24 h to react at the hydrogen atmosphere 1-100 atm to obtain optical active chiral δ-hydroxyl esters and corresponding chiral 1 claim 2 ,5-diols.9. The kinetic resolution method of racemic δ-hydroxyl esters via asymmetric catalytic hydrogenation according to - claim 2 , wherein claim 2 , the said base is alcohol alkalis claim 2 , ...

CHIRAL RESOLUTION METHOD OF N-[4-(1-AMINOETHYL)-PHENYL]-SULFONAMIDE DERIVATIVES

The present specification relates to a chiral resolution method of a stereoisomer mixture, comprising a step of mixing a stereoisomer mixture of compounds, in which an amine group is bound to an asymmetric carbon atom, with a chiral auxiliary and salt-forming auxiliary compound, wherein the chiral auxiliary is an O,O′-diacyltartaric acid derivative, more specifically, a 2,3-dibenzoyl-tartaric acid or O,O′-di-p-toluoyl tartaric acid, the salt-forming auxiliary compound is mandelic acid or camphorsulfonic acid, and an optical isomer having a high level of optical purity can be obtained by using the method. Therefore, according to one aspect of the present invention, the method can be useful in pharmaceutical or cosmetic field when preparing an optical isomer having a high optical purity. 2. The method according to claim 1 , wherein the chiral auxiliary is one or more selected from a group consisting of 2 claim 1 ,3-dibenzoyltartaric acid claim 1 , O claim 1 ,O′-di-p-toluoyltartaric acid claim 1 , a stereoisomer thereof claim 1 , and a combination thereof and the auxiliary salt-forming compound is one or more selected from a group consisting of mandelic acid claim 1 , camphorsulfonic acid claim 1 , a stereoisomer thereof claim 1 , and a combination thereof.3. The method according to claim 1 , wherein Ris hydrogen and an R enantiomer of the compound of formula (I) is obtained in enantiomeric excess when the chiral auxiliary is selected from a group consisting of the (+)-2 claim 1 ,3-dibenzoyl-D-tartaric acid claim 1 , (+)-O claim 1 ,O′-di-p-toluoyl-D-tartaric acid and a combination thereof.4. The method according to claim 1 , wherein Ris hydrogen and an S enantiomer of the compound of formula (I) is obtained in enantiomeric excess when the chiral auxiliary is selected from a group consisting of the (−)-2 claim 1 ,3-dibenzoyl-L-tartaric acid claim 1 , (−)-O claim 1 ,O′-di-p-toluoyl-L-tartaric acid and a combination thereof.5. The method according to claim 1 , wherein the ...

Stereoisomer of bromadiolone, composition and rodenticidal bait comprising same, and process for controlling target rodent pests

Disclosed is a configurational stereoisomer, named enantiomer E3, of bromadiolone having, by chromatographic analysis of a bromadiolone composition including four configurational stereoisomers of bromadiolone performed under the conditions described hereinbelow, a retention time t3 having a value such that t1<t2<t3<t4; t1, t2 and t4 being the retention times of the configurational stereoisomers of bromadiolone different from the enantiomer E3, the analysis being performed at a temperature of 27.3° C.

STEREOISOMER OF BROMADIOLONE, COMPOSITION AND RODENTICIDE BAIT COMPRISING SAME, AND METHOD FOR CONTROLLING TARGET RODENT PESTS

Disclosed is a configurational stereoisomer, named enantiomer E, of bromadiolone having, by chromatographic analysis of bromadiolone including four configurational stereoisomers of bromadiolone performed under the conditions described below, a retention time thaving a value such that t Подробнее

METHOD FOR PRODUCING PYRROLE DERIVATIVE, AND INTERMEDIATE THEREOF

The present invention provides a method for producing an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, and an intermediate thereof. A method for producing an atropisomer of a pyrrole derivative using a compound represented by (B) [wherein Rrepresents a C1-C4 alkyl group, and Rrepresents a 2-hydroxyethyl group or a carboxymethyl group] as a production intermediate. 2. The method according to claim 1 , wherein the reagent is a Grignard reagent.3. The method according to claim 1 , wherein the Grignard reagent is selected from ethylmagnesium bromide claim 1 , ethylmagnesium chloride claim 1 , isopropylmagnesium chloride claim 1 , methylmagnesium bromide claim 1 , and phenylmagnesium bromide.4. The method according to claim 1 , wherein the Grignard reagent is ethylmagnesium bromide.5. The method according to claim 2 , wherein the reaction solvent is tetrahydrofuran.6. The method according to claim 2 , wherein reacting ethyl (S)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate with the Grignard reagent is carried out at a reaction temperature from room temperature to 150° C.7. The method according to claim 6 , wherein the reaction temperature is from 60° C. to 100° C.8. The method according to claim 2 , wherein reacting ethyl (S)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylate with the Grignard reagent is carried at a reaction time from 0.5 to 5 hours.9. The method according to claim 8 , wherein the reaction time is from 0.5 to 2 hours.10. The method according to claim 1 , wherein the reagent is a metal alkoxide.11. The method according to claim 1 , wherein the metal alkoxide is selected from potassium t-butoxide claim 1 , sodium t-butoxide claim 1 , sodium methoxide claim 1 , and potassium ethoxide.12. The method according to claim 10 , wherein the reaction solvent is selected from tetrahydrofuran claim 10 , toluene claim 10 , dimethylsulfoxide ...

STEREOISOMER OF FLOCOUMAFEN, COMPOSITION AND RODENTICIDE BAIT COMPRISING SAME, AND METHOD FOR CONTROLLING TARGET RODENT PESTS

Disclosed is a configurational stereoisomer, named enantiomer E, of flocoumafen, the enantiomer Ehaving, by chromatographic analysis of flocoumafen performed under particular conditions, a retention time thaving a value such that t Подробнее

Method for producing lacosamide and intermediate thereof

The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.

Thermally immobilized polysaccharide derivatives

The invention essentially relates to thermally crosslinked polysaccharide derivatives which contained no polymerizable functional groups prior to crosslinking and which are used in particular as support materials for the chromatographic separation of enantiomers. The present invention relates to thermally crosslinked polysaccharide derivatives in which the OH groups, as OR groups, have been esterified or converted into a carbamate (urethane), or mixtures of these, with the proviso that the OR groups contained no polymerizable double bonds prior to crosslinking. The thermally crosslinked polysaccharides according to the invention in conditioned form can also be used as pure polymers for the chromatographic separation of enantiomers.

Verfahren zur trennung verbindungsbildender chiraler systeme

Die Erfindung betrifft ein Verfahren zur Racemattrennung für verbindungsbildende Substanzen. Bei diesem Verfahren wird in einem Verfahrensschritt wenigstens eine mit einem Enantiomer angereicherte Fraktion erzeugt. Schließlich wird an der Fraktion eine bevorzugte Kristallisation durchgeführt.

Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

The present invention relates to a process for the preparation of (1 R,2R)-3- dimethylamino-1-ethyl-2-methyl-propyl)-phenol.

New process for the synthesis of tapentadol and intermediates thereof

The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. A further object of the present invention is constituted by the tapentadol free base in solid form, obtainable by means of the process of the invention. Still another object of the invention is represented by the crystalline forms I and II of the tapentadol free base. A further object of the present invention is the mixture of the crystalline forms I and II of the tapentadol free base.

Molecularly imprinted beaded polymers and stabilized suspens ion polymerization of the same in perfluorocarbon liquids

The claimed invention is directed to a molecularly imprinted support formed from at least two distinct acylic monomers and at least one imprinted molecule. The support comprises beads having a uniform surface for reproducible presentation thereon.

Stabilizers, polymers, and emulsions useful for molecular imprinting technology

The claimed invention is directed to stabilizers, polymers, and emulsifiers useful in preparing molecularly imprinted materials having recognition capabilities corresponding to the imprint molecule.

Supports useful for molecular imprinting technology

The claimed invention is directed to a molecularly imprinted support formed from at least two distinct acylic monomers and at least one imprinted molecule. The support comprises beads having a uniform surface for reproducible presentation thereon.

Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol

The present invention relates to a process for the preparation of (1R,2R)- 3 -dimethylamino- 1 -ethyl- 2 -methyl-propyl)-phenol.

Active-energy-ray-curable composition, method for manufacturing three-dimensional shaped object, and device for manufacturing three-dimensional shaped object

Arylcyclohexylamine derivatives and their use in the treatment of psychiatric disorders

Provided herein are arylcyclohexylanine derivatives and their use in the treatment of psychiatric disorders.