Abstract

The present application concerns a novel process suitable for synthesizing buprenorphine and the novel intermediates products involved by said process, as well as the buprenorphine and derivatives thereof obtainable by said process.

IPC Classes  ?

• C07D 489/12 - Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14 the bridge containing only two carbon atoms
• A61P 25/04 - Centrally acting analgesics, e.g. opioids
• A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine

Abstract

The present invention relates to a process for the preparation of iloprost of formula I through new intermediates, isolation of iloprost of formula I in solid form, as well as preparation of the 16(S)-iloprost and 16(R)-iloprost isomers of formulae (S)-I and (R)-I and isolation of iloprost of formula I and 16(S)-iloprost of formula (S)-I in solid, crystalline form.

IPC Classes  ?

• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 67/31 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
• C07C 59/46 - Unsaturated compounds containing hydroxy or O-metal groups containing rings other than six-membered aromatic rings
• C07C 69/608 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety

Abstract

The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S), 16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S), 16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.

IPC Classes  ?

• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Abstract

A process of preparing compounds of general formula I, by cuprate coupling of a vinyl cuprate of general formula II with a protected enone of general formula IV to produce a compound of general formula (V) removing the protecting groups of the compound of general formula (V) and purifying the compound of general formula (I) by chromatography; wherein the vinyl cuprate of formula (II) is prepared by reacting a vinyl stannane of formula III with copper halide CuX and alkyllithium R1Li and wherein an excess of the alkyllithium is decomposed before the said coupling reaction.

IPC Classes  ?

• C07C 69/738 - Esters of keto-carboxylic acids
• C07F 7/22 - Tin compounds
• C07F 1/08 - Copper compounds
• C07C 45/00 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds

Abstract

The invention provides a new enzimatic process for the preparation of chiral carboxylic acids, their salts and acid derivatives of the general formula (I) by enzymatic hydrolysis of racemic carboxylic acid ester of the general formula (II) and optionally subsequent esterification or acylation.

IPC Classes  ?

• C12P 7/62 - Carboxylic acid esters
• C07F 9/40 - Esters thereof
• C12P 7/40 - Preparation of oxygen-containing organic compounds containing a carboxyl group
• C12P 41/00 - Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
• C07C 57/18 - Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon triple bonds as unsaturation
• C07C 69/24 - Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds

Abstract

The invention provides a stable epoprostenol sodium and a process for the preparation this pharmaceutically active ingredient.

IPC Classes  ?

• C07D 307/937 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
• A61K 9/19 - Particulate form, e.g. powders lyophilised

Abstract

The present invention relates to a process for the preparation of iloprost of formula I through new intermediates, isolation of iloprost of formula I in solid form, as well as preparation of the 16(S)-iloprost and 16(R)-iloprost isomers of formulae (S)-I and (R)-I and isolation of iloprost of formula I and 16(S)-iloprost of formula (S)-I in solid, crystalline form.

IPC Classes  ?

• C07C 59/46 - Unsaturated compounds containing hydroxy or O-metal groups containing rings other than six-membered aromatic rings
• C07C 69/608 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety

Abstract

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

IPC Classes  ?

• C07C 51/347 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups
• C07C 41/26 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
• C07C 45/30 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/41 - Preparation of salts of carboxylic acids by conversion of the acids or their salts into salts with the same carboxylic acid part
• C07C 67/14 - Preparation of carboxylic acid esters from carboxylic acid halides
• C07C 67/29 - Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
• C07C 67/293 - Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton
• C07C 69/76 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring
• C07C 41/30 - Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
• C07C 41/48 - Preparation of compounds having groups
• C07C 43/315 - Compounds having groups containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms
• C07C 13/547 - Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings at least one ring not being six-membered, the other rings being at the most six-membered
• C07C 35/37 - Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with a hydroxy group on a condensed ring system having three rings
• C07C 59/72 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings

Abstract

The invention provides a new process for the preparation of optically active Beraprost of formula (I) starting from racemic Beraprost alkyl ester through hydrolysis, enantiomer esterification, preparation of diacyl-Beraprost ester diastereomers and their separation and hydrolysis.

IPC Classes  ?

• C07D 307/93 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered

Abstract

The subject of the invention is a process for the preparation of Latanoprostene bunod of formula (I) with a purity higher than 95% where chromatography is used applying normal phase gravity silica gel column chromatography where the used silica gel is irregular silica gel or spherical silica gel an as eluent and eluent mixture consisting of an apolar and a polar solvent is used and if desired, contamination of the purified compound of formula I arising from the solvents are removed by silica gel filtration chromatography.

IPC Classes  ?

• 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
• B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography

Abstract

The subject of the invention is a novel process for the preparation of Carboprost tromethamine salt where alkylation the enone of the general formula (II) is carried out in the presence of a chiral auxiliary in aprotic solvent with a Grignard reagent. The methyl ester epimers of formula (VII) are separated by gravity silica gel chromatography and the salt formation is carried out by using solid tromethamine base.

IPC Classes  ?

• 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
• B01D 15/26 - Selective adsorption, e.g. chromatography characterised by the separation mechanism
• B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
• B01J 20/10 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
• C07C 7/12 - Purification, separation or stabilisation of hydrocarbonsUse of additives by adsorption, i.e. purification or separation of hydrocarbons with the aid of solids, e.g. with ion-exchangers

Abstract

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

IPC Classes  ?

• C07C 51/347 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups
• C07C 41/26 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
• C07C 45/30 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/41 - Preparation of salts of carboxylic acids by conversion of the acids or their salts into salts with the same carboxylic acid part
• C07C 67/14 - Preparation of carboxylic acid esters from carboxylic acid halides
• C07C 67/29 - Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
• C07C 67/293 - Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton
• C07C 69/76 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring
• C07C 41/30 - Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
• C07C 41/48 - Preparation of compounds having groups
• C07C 43/315 - Compounds having groups containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms
• C07C 13/547 - Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings at least one ring not being six-membered, the other rings being at the most six-membered
• C07C 35/37 - Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with a hydroxy group on a condensed ring system having three rings
• C07C 59/72 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings

Abstract

The subject of the invention is a process for the preparation of Latanoprostene bunod of formula (1) with a purity higher than 95% where chromatography is used applying normal phase gravity silicagel column chromatography where the used silicagel is irregular silicagel or spherical silicagel an as eluent and eluent mixture consisting of an a polar and a polar solvent is used and if desired, contamination of the purified compound of formula I arising from the solvents are removed by silicagel filtration chromatography. The Latanoprostene bunod of formula (I) is as follows:

IPC Classes  ?

• 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

Abstract

3, wherein the crude prostaglandin acid of the general formula II is purified by normal phase silicagel chromatography.

IPC Classes  ?

• 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
• B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction

Abstract

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, n group or O atom or S atom, and where n=0-3.

IPC Classes  ?

• 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
• C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
• C07D 209/50 - Iso-indolesHydrogenated iso-indoles with oxygen and nitrogen atoms in positions 1 and 3

Abstract

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, n group or O atom or S atom, and where n=0-3.

IPC Classes  ?

• 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
• C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• C07D 209/50 - Iso-indolesHydrogenated iso-indoles with oxygen and nitrogen atoms in positions 1 and 3
• C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Abstract

The subject of the invention is process the preparation of travoprost of formula (I) characterized by that the free acid of formula (II) is a.) activated with 2-chloro-1,3-dimethyl-imidazolinium chloride (DMC) and the resulting activated carboxylic acid intermediate is reacted with isopropyl alcohol, or b.) reacted with alkyl haloformate and the resulting mixed anhydride is reacted with isopropyl alcohol, or c.) activated with a straight or branched C1-8 dialkyl dicarbonate and reacted with isopropanol in the presence of water-free magnesium salt.

IPC Classes  ?

• C07C 67/42 - Preparation of carboxylic acid esters by oxidation of groups which are precursors for the acid moiety of the ester by oxidation of secondary alcohols or ketones
• 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

Abstract

The invention relates to a process for the preparation of travoprost of formula (I), comprising that, the compound of formula (II), is stereoselectively reduced, the resulting compound of formula (III), is if desired crystallized, the lactone group of the compound of formula (III) is reduced, the p-phenyl-benzoyl protecting group of the thus obtained compound of formula (IV), is removed, the resulting triol of formula (V), is, if desired after crystallization, transformed by Wittig reaction into the acid of formula (VI), which is then esterified.

IPC Classes  ?

• C07D 407/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group
• C07C 67/333 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
• 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
• C07D 307/937 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins

Abstract

n group or 0 atom or S atom, and where n=0-3.

IPC Classes  ?

• C07C 69/74 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
• C07C 231/00 - Preparation of carboxylic acid amides
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• 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
• C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
• C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
• C07D 209/50 - Iso-indolesHydrogenated iso-indoles with oxygen and nitrogen atoms in positions 1 and 3

Abstract

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, - where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R1 and R2 independently represent hydrogen atom or a straight or branched C1-10 alkyl- or aralkyl- group, optionally substituted with -ONO2 group, or an aralkyl- or aryl- group, which contains heteroatom, R3 represents a straight or branched, saturated or unsaturated C4-6 hydrocarbon group, or a C4-10 alkylcycloalkyl- or cycloalkyl- group, or an optionally with alkyl group or halogen atom substituted phenyl-, C7-10 alkylaryl- or hetaryl- group, Y represents (CH2)n group or 0 atom or S atom, and where n=0-3.

IPC Classes  ?

• 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
• C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Abstract

ABSTRACT The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, - where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R1 and R2 independently represent hydrogen atom or a straight or branched C1-10 alkyl- or aralkyl- group, optionally substituted with -0NO2 group, or an aralkyl- or aryl- group, which contains heteroatom, R3 represents a straight or branched, saturated or unsaturated C4-6 hydrocarbon group, or a C4-10 alkylcycloalkyl- or cycloalkyl- group, or an optionally with alkyl group or halogen atom substituted phenyl-, C7-10 alkylaryl- or hetaryl- group, Y represents (CH2)n group or 0 atom or S atom, and where n=0- 3. Date Recue/Date Received 2020-09-28

IPC Classes  ?

• 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
• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Abstract

The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S),16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S),16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.

IPC Classes  ?

• C07D 307/935 - Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans