This invention provides processes for preparation of 3-alkyl indoles of Formula 1 : wherein A1, A2 and A3 are independently selected from the group consisting of: H, X, OR1, CN, CONR22 and C02R3; R1 is C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl; LG is a leaving group; X is a halogen; and n is 1, 2 or 3.
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Provided for in the instant application are two additional forms of rifaximin, namely rifaximin polymorphic forms ΑΡΟ-III and APO-IV. Also provided are allegedly novel processes for preparing the previously disclosed rifaximin polymorphic forms APO-I and ΑΡΟ-II. Rifaximin is a non-aminoglycoside antibiotic that has previously been found to be useful for the treatment of traveller's diarrhea caused by Escherichia coli bacteria, as well as in the treatment of irritable bowel syndrome, diverticular disease, hepatic encephalopathy, pyogenic skin infections and as an antibacterial prophylactic prior to colon surgery.
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
3.
DIMETHYL-(3,3-DIFLUORO-2,2-DIHYDROXYHEPTYL)PHOSPHONATE AND PROCESSES FOR ITS PREPARATION
A compound dimethyl-(3,3-difluoro-2,2-dihydroxyheptyl)phosphonate (I), a crystalline form of this compound, processes for its preparation, and use of this compound in the preparation of prostaglandin derivatives such as Lubiprostone.
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
4.
A PROCESS FOR THE PREPARATION OF LAPATINIB AND ITS DITOSYLATE SALT
There is provided processes for preparing Lapatinib and pharmaceutically acceptable salts thereof by the reductive amination of the aldehyde of Formula II by treatment with 2-methanesulphonylethylamine followed by catalytic hydrogenation in the presence of a suitable hydrogenation catalyst.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
5.
PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
Provided are process for the preparation of (R)- and/or (S)- Rivaroxaban, and compounds which are intermediate compounds used in the processes for the preparation of (R)- and/or (S)-Rivaroxaban.
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 265/32 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
6.
PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
Provided are process for the preparation of (R)- and/or (S)- Rivaroxaban, and compounds which are intermediate compounds used in the processes for the preparation of (R)- and/or (S)-Rivaroxaban.
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 265/32 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Provided for in the instant application are two additional polymorphic forms of rifaximin; namely substantially pure APO-I and ΑΡΟ-Π. Also provided are processes for preparing substantially pure APO-I and ΑΡΟ-Π. Rifaximin is a non-aminoglycoside antibiotic that has previously been found to be useful for the treatment of traveller's diarrhea caused by Escherichia coli bacteria, as well as in the treatment of irritable bowel syndrome, diverticular disease, hepatic encephalopathy, pyogenic skin infections and as an antibacterial prophylactic prior to colon surgery.
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
8.
POLYMORPHIC FORMS OF WARFARIN POTASSIUM AND PREPARATIONS THEREOF
There is provided crystalline solvate forms of Warfarin potassium, termed APO-I and APO-II, and processes for making APO-I and APO-II. APO-I and APO-II are polymorphic solvate forms of Warfarin potassium.
C07D 311/56 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 without hydrogen atoms in position 3
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
9.
POLYMORPHIC FORMS OF LAPATINIB DITOSYLATE AND PROCESSES FOR THEIR PREPARATION
There is provided a crystalline form of Lapatinib, termed APO-I, and methods for making APO-I. There is also provided a crystalline solvate form of Lapatinib, termed APO-II, and methods for making APO-II.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07C 309/30 - Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
C30B 7/08 - Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by cooling of the solution
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
A61K 31/558 - Eicosanoids, e.g. leukotrienes having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
There is provided processes for purification of Lubiprostone by formation of amine salts. Also provided are compounds of the Lubiprostone amine salt. Also provided are compositions comprising Lubiprostone and amines.
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
A61K 31/558 - Eicosanoids, e.g. leukotrienes having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
12.
FORMS OF DEXLANSOPRAZOLE AND PROCESSES FOR THE PREPARATION THEREOF
Provided is dexlansoprazole propylene glycolate hydrate. Polymorphic forms thereof are also provided. The dexlansoprazole propylene glycolate hydrate maybe such that the propylene glycol component is present in approximately equal proportions of (R) absolute configuration and (S) absolute configuration, or present in predominantly (R) absolute configuration, or predominantly (S) absolute configuration. Salts of dexlansoprazole are also provided. In particular, crystalline dexlansoprazole isopropylammonium salt and crystalline MTBE solvate of dexlansoprazole t-butylammonium salt are provided. Pharmaceutical formulations comprising dexlansoprazole propylene glycolate hydrate are also provided. Furthermore, processes for preparation of dexlansoprazole propylene glycolate hydrate are provided.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
Provided are process for the preparation of (R)- and/or (S)-Rivaroxaban, and compounds which are intermediate compounds used in the processes for the preparation of (R)- and/or (S)-Rivaroxaban.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
14.
METHODS OF MAKING EFAVIRENZ AND INTERMEDIATES THEREOF
The present invention is directed to methods of preparation of Efavirenz ( 1 ),various intermediates useful in the preparation of Efavirenz and methods of preparation of such intermediates hi some embodiments, a stereoselective cyclopropylacetylide addition reaction may be controlled by introduction of an appropriate chiral carbonyl auxiliary group on the aniline nitrogen The product of such an aymmetric addition (5) may then undergo a cyclization reaction with concomitant removal of the chiral auxiliary group, without the need for a discrete deprotection step. Formulae (I), (II).
C07C 235/38 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
C07C 235/88 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having the nitrogen atom of at least one of the carboxamide groups further acylated
C07D 265/18 - 1,3-OxazinesHydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
15.
PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
This invention provides a process for the preparation of S-Rivaroxaban and/or R- Rivaroxaban comprising reacting, in the presence of a first base, a compound of Formula (9): with a compound of Formula (8).
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
16.
PROCESSES FOR THE PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
This invention provides a process for the preparation of S-Rivaroxaban and/or R- Rivaroxaban comprising reacting, in the presence of a first base, a compound of Formula (9): with a compound of Formula (8).
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
17.
METHODS OF MAKING LUBIPROSTONE AND INTERMEDIATES THEREOF
There is provided processes for preparing Lubiprostone and intermediates thereof. Also provided are compounds, including intermediates for preparing Lubiprostone as well as compositions comprising Lubiprostone and other compounds, including intermediates for preparing Lubiprostone and other compounds. (I)
C07C 59/66 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
18.
POLYMORPHIC FORM OF 5-CHLORO-N-{[(5S)-2-OXO-3-[4-(3-OXOMORPHOLIN-4-YL)PHENYL]OXA-ZOLIDIN-5-YL]-METHYL}THIOPHENE-2-CARBOXAMIDE
A polymorphic form of rivaroxaban, 5-chloro-N-{[(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]oxa-zolidin-5-yl]- methyl}thiophene-2-carboxamide (termed form APO-A), processes for the preparation thereof, and compositions and formulations comprising form APO-A are provided. Also provided are compositions comprising a crystalline form of rivaroxaban and solvents selected from C3 to C6 ketones, C3 to C4 amides and mixtures thereof.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
19.
PROCESSES FOR THE PREPARATION OF ERLOTINIB HYDROCHLORIDE
There is provided processes to prepare erlotinib hydrochloride. The processes may comprise exposing solid erlotinib free base containing residual solvent to hydrogen chloride gas. The processes may comprise spraying hydrogen chloride gas in an organic solvent onto solid erlotinib free base. Erlotinib hydrochloride prepared by such methods is also provided.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
20.
IMPROVED PROCESSES FOR THE SYNTHESIS OF OLANZAPINE
There is provided a process for the preparation of olanzapine comprising: i) reacting 4-amino-2-methyl-10H-thieno-[2, 3- b][1,5]benzodiazepine and N-methylpiperazine in a C1 to C4 alcoholic solvent or mixture thereof at suitable temperature and for a suitable time, ii) cooling the reaction mixture, and iii) isolating the precipitated olanzapine.
A process for obtaining crystalline Form-I olanzapine comprising the following: a) dissolving crude olanzapine in a solvent to form a solution, b) optionally drying by azeotropic distillation to remove water, c) precipitating by adding the solution of step (a) to an antisolvent, and d) isolating the precipitated crystalline Form-I olanzapine by filtration and drying at ambient temperature.
The present invention relates to a process for producing 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones of formula (1) , including Finasteride and Dutasteride.
The present application relates to atorvastatin calcium propylene glycol solvates and processes of preparing the same. The atorvastatin calcium propylene glycol solvates are crystalline and show high chemical and solid state stability, low hygroscopicity, and good flow properties.The solvates can be efficiently prepared from various forms of atorvastatin and either (R), (S), or mixtures of (R) and (S) propylene glycol, and may be easily filtered and dried on an industrial scale.
C07D 207/34 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
24.
IBANDRONATE SODIUM PROPYLENE GLYCOL SOLVATE AND PROCESSES FOR THE PREPARATION THEREOF
Ibandronate sodium and propylene glycol readily forms a free-flowing crystalline solvate. The novel solvate is non-hygroscopic, free-flowing, chemically and polymorphically stable, and easily dried even on industrial scale. Thus, it is particularly suitable for pharmaceutical applications. A process for preparing said novel solvate is further disclosed. Formula (I).
A novel process for the preparation of omeprazole and its enantiomers, such as esomeprazole, as well as the preparation of related 2-(2-pyridinylmethyl-sulphinyl)-1H-benzimidazoles, including pantoprazole, lansoprazole and rabeprazole, as recemates or single enantiomers, and their alkali or alkaline salts has been developed. The novel process involves the surprising discovery that protection of the free-base benzimidazole sulfoxide (e.g. omeprazole or esomeprazole), by reaction with an alkyl, aryl or aralkyl chloroformate following oxidation of the corresponding sulfide, eliminates the need for its direct isolation. Subsequent removal of the protecting group with a solution of alkali or alkaline earth alkoxide in a C1-C4 alcohol directly provides the corresponding salt. By eliminating the need to handle the free-base benzimidazole sulfoxide, this advantageous procedure provides increased chemical yields over processes described in the art.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A process for the preparation of aminoalkyl phenyl carbamate compounds of Formula I, wherein R1 and R2 independently are hydrogen or a C1-6 alkyl; R3 and R4 are the same or different and each is a C1-6 alkyl; or R3 and R4 together with the nitrogen to which they are attached form a cyclic three to eight membered ring, with or without a heteroatom like nitrogen or oxygen; R5 and R6 independently are hydrogen, linear, branched or cyclic C1-6 alkyl; or R5 and R6 together with the nitrogen to which they are attached form a cyclic three to eight membered ring, with or without a heteroatom like nitrogen or oxygen; the carbon centre designated '*' can be racemic or enantiomerically enriched in the (R)- or (S)- configuration; and pharmaceutically acceptable acid addition salts thereof.
C07C 269/04 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
C07C 271/42 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
A process which includes the reacting of sodium perborate with N-⏧4-cyano-3-(trifluoromethyl)phenyl]-3-⏧(4-fluorophenyl)thio]-2-hydroxy- 2-methylpropanamide to form bicalutamide. Said process may comprise the reaction of N-⏧4-cyano-3-(trifluoromethyl)phenyl]-2- methyloxiranecarboxamide with 4-fluorobenzenethiol in the presence of a base, water and a first solvent that is water miscible to form N-⏧4- cyano-3-(trifluoromethyl)phenyl]-3-⏧(4-fluorophenyl)thio]-2-hydroxy-2-methylpropanamide, and reacting the N-⏧4-cyano-3- (trifluoromethyl)phenyl]-3-⏧(4-fluorophenyl)thio]-2-hydroxy-2-methylpropanamide with sodium perborate in a second solvent. The process is efficient, inexpensive, environmentally friendly and produces bicalutamide in good yield.
C07C 317/50 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the nitrogen atoms being part of any of the groups X being a hetero atom, Y being any atom
28.
AN EFFICIENT METHOD FOR PREPARING 3-ARYLOXY-3- ARYLPROPYLAMINES AND THEIR OPTICAL STEREOISOMERS
Provided is an efficient method for the preparation of 3-aryloxy-3- arylpropylamines, their optical stereoisomers, and pharmaceutically acceptable salts thereof. The process allows for the isolation of 3-aryloxy-3- arylpropylamines in high yield and purity. The present invention further relates to a process for producing fluoxetine, tomoxetine, norfluoxetine, duloxetine, nisoxetine, and their optically enriched (R)- and (S)-enantiomers.
C07C 217/54 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
C07C 213/02 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
C07D 333/20 - Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
29.
PREPARATION OF ACID ADDITION SALTS OF ZIPRASIDONE AND INTERMEDIATES THEREOF BY SOLID PHASE-GAS PHASE REACTIONS
A process for the preparation of an acid addition salt of ziprasidone base and intermediates thereof comprising exposing the ziprasidone base in solid form to a gaseous acid in a substantially dry environment. The process is solvent free and the gaseous acid is mixed with one or more inert gases. The process produces ziprasidone hydrochloride in high yield and purity and is reliable, consistent and suitable for large scale manufacturing. The process can also be used to prepare ziprasidone hydrobromide and ziprasidone acetate.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
30.
PREPARATION OF ACID ADDITION SALTS OF AMINE BASES BY SOLID PHASE-GAS PHASE REACTIONS
A process for the preparation of an acid addition salt of an organic base comprising exposing the organic base in solid form to a gaseous acid, with the proviso that ziprasidone, its acid addition salts and intermediates thereof are excluded.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 307/52 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/4458 - Non-condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A process is provided for preparing pharmaceutical grade atorvastatin hemicalcium salt comprising: (a) deesterifying, (Formula I), wherein R is an ester protecting group to (Formula II), (b) extracting R(R*,R*)-3 into an organic solvent or mixture of solvents, (c) adding a base of formula NR1R2R3 wherein R1, R2 and R3 are independently selected from H, substituted or non-substituted C1 to C7 alkyl, C6 to C9 aryl, C8 to C10 aralkyl or aminoalkyl to form atorvastatin base salt, (d) isolating by precipitation of the above atorvastatin base salt and purifying when necessary, (e) converting atorvastatin base salt to atorvastatin hemicalcium salt by treatment with a calcium salt solution, and (f) isolating the atorvastatin hemicalcium salt.
C07D 207/34 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
32.
AN IMPROVED PROCESS FOR THE PREPARATION OF ATORVASTATIN AND INTERMEDIATES
A process is provided for preparing (R)-5-⏧2-(4-fluorophenyl)-5-(l- methylethyl)-3-phenyl-4-⏧(phenylamino)carbonyl]-lH-pyrrol-l-yl]-5-hydroxy-3-oxo- 1-heptanoic acid, R-substituted ester 9 comprising: (a) reacting 5-(4-fluorophenyl)-2-(l -methylethyl)-l -(3-oxopropyl)-N,4- diphenyl-lH-pyrrole-3-carboxamide, 1, with the enolate form of (S)-2- hydroxy- 1 ,2,2-triphenylethyl acetate substituent in a chelating co- solvent; (b) hydrolysis of (R,S)-5-⏧2-(4-fluorophenyl)-5-(l -methylethyl)-3-phenyl- 4-⏧(phenylamino)carbonyl]- 1 H-pyrrol- 1 -yl]-3-hydroxy- 1 -pentanoic acid, (S)-2 -hydroxy- 1 ,2,2-triphenylethyl ester (2a and 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the (R,S)-5-⏧2-(4-fluorophenyl)-5-(l -methylethyl)-3-phenyl-4- ⏧(phenylamino)carbonyl]- 1 H-pyrrol- 1 -yl]-3 -hydroxy- 1 -pentanoic acid, 7; (c) treating the carboxylic acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt; (d) alkylation of the (R)-7 chiral base salt or the free acid derived from (R)-7, forming (R)-5-⏧2-(4-fluorophenyl)-5-(l-methylethyl)-3-phenyl- 4-⏧(phenylamino)carbonyl]-lH-pyrrol-l-yl]-5-hydroxy-3-oxo-l- heptanoic acid, R-substituted ester 9, wherein the R substituent is a Cl to C6 alkyl, C6 to C9 aryl or C7 to Cl0 aralkyl. Subsequently, R-substituted ester 9 may be converted into atorvastatin calcium 6 based on procedures known in the art.
C07D 207/34 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
patents
