Abrégé

A process for preparing obeticholic acid, wherein the 7-keto-litocholic acid amide of formula (II), where R1, R216566 cycle and the protecting group on the hydroxyl in position 3 is a carbamoyl with the same substitution as the amide, is converted to the 7-trimethylsilyl enol ether of formula (III), which is then converted by reaction with an alkylation agent to the 6-ethylidene-derivative of formula (IV), which is hydrogenated to the compound of formula (V) and then simultaneously deprotected in position 3 and hydrolysed to the compound of formula (VI) and then reduced to obeticholic acid of formula (VII).

Classes IPC  ?

• C07J 9/00 - Stéroïdes normaux contenant du carbone, de l'hydrogène, un halogène ou de l'oxygène, substitués en position 17bèta par une chaîne de plus de deux atomes de carbone, p. ex. cholane, cholestane, coprostane
• C07J 41/00 - Stéroïdes normaux contenant un ou plusieurs atomes d'azote n'appartenant pas à un hétérocycle
• C07J 51/00 - Stéroïdes normaux à squelette du cyclopenta[a]hydrophénanthrène non modifié non prévus dans les groupes

Abrégé

A new polymorph of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine (designated as polymorph E), of formula I, characterized by an X-ray diffraction pattern of X-RPD showing the following reflections at 2 Theta = 5.8°, 12.3°, 15.9°, 17.3°, 20.5°, 22.6°, 23.6°, 27.7°, and 29.2°, and further characterized by DSC showing marked endotherm in the range of 258 to 264 °C, and further characterized by IR spectra, which is prepared by a procedure comprising the following operations: • a. Mixing of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine with a polar aprotic solvent, preferably with dimethylsulfoxide, and heating to form a saturated solution; • b. Cooling of the saturated solution with formation of a turbid solution of 2-[4: [(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine; • c. Addition of the turbid solution of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-l-yl]adenosine to a protic solvent, preferably methanol, with separation of a gel-like precipitate; • d. Heating of the separated gel-like precipitate in the protic solvent to the boil with formation of a suspension of polymorph E; • e. Cooling of the suspension, isolation and drying of polymorph E.

Classes IPC  ?

• C07H 19/167 - Radicaux purine avec un ribosyle comme radical saccharide
• C07H 1/00 - Procédés de préparation des dérivés du sucre

Abrégé

The invention relates to a compound which is, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine, which is a selective A2A adenosine receptor agonist in myocardial imaging. The new polymorph of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine (designated as polymorph E) is characterized by an X-ray diffraction pattern of X-RPD showing the following reflections at 2 Theta=5.8°, 12.3°, 15.9°, 17.3°, 20.5°, 22.6°, 23.6°, 27.7°, and 29.2°; and further characterized by a DSC scan showing marked endotherm in the range of 258 to 264° C.; and further characterized by a specific IR spectra. The invention further relates to a method of preparing the polymorph by recrystallization from other polymorphic forms of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine by a procedure comprising the following operations: mixing of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine with a polar aprotic solvent, preferably with dimethylsulfoxide, and heating to form a saturated solution; cooling of the saturated solution with formation of a turbid solution of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine; addition of the turbid solution of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine to a protic solvent, preferably methanol, with separation of a gel-like precipitate; heating of the separated gel-like precipitate in the protic solvent to a boil with formation of a suspension of polymorph E; and cooling of the suspension, isolation and drying of polymorph E.

Classes IPC  ?

• C07H 19/00 - Composés contenant un hétérocycle partageant un hétéro-atome du cycle avec un radical saccharideNucléosidesMononucléotidesLeurs anhydro-dérivés
• C07H 19/19 - Radicaux purine avec un arabinosyle comme radical saccharide
• C07H 19/16 - Radicaux purine
• C07H 1/06 - SéparationPurification
• C07H 1/00 - Procédés de préparation des dérivés du sucre
• C07H 19/167 - Radicaux purine avec un ribosyle comme radical saccharide

Abrégé

The present invention describes a novel process for the preparation of Moxonidine (Formula (I)).

Classes IPC  ?

• C07D 403/12 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons

Abrégé

A method for the' preparation of 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1- yl]adenosine monohydrate of formula I by reaction of 2-(4-methoxycarbonylpyrazol-1-yl) adenosine of formula III with a solution of methylamine in a non-aqueous solvent, optionally in combination with another inert solvent, to produce anhydrous 2-[4-[(methylamino)carbonyl]- 1-H-pyrazol-1-yl]adenosine, which is converted to 2-[4-[(methylamino)carbonyl]-1-H - pyrazol-1-yljadenosine monohydrate of formula I by addition of water.

Classes IPC  ?

• C07H 19/167 - Radicaux purine avec un ribosyle comme radical saccharide

Abrégé

A method for the preparation of 2-(4-methoxycarbonylpyrazol-l-yl)adenosine of formula la and 2-(4-ethoxycarbonylpyrazol-l-yl)adenosine of formula lb by reaction of 2- hydrazinoadenosine of formula III and the sodium salt of 3,3-dimethoxy-2- methoxycarbonylpropen- l-ol of formula Va or the sodium salt of 3,3-diethoxy-2- ethoxycarbonylpropen-l -ol of formula Vb in combination with a solvent and an acidic agent.

Classes IPC  ?

• C07H 19/167 - Radicaux purine avec un ribosyle comme radical saccharide

Abrégé

Highly optically pure 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin- 5-yl} methyl)- lH-isoindol- l,3(2H)-dione (I) is obtained by reaction of 2-((2R)-2-hydroxy-3-[4-(3- oxo-4-moφholinyl)phenyl]amino-propyl)- lH-isoindol- l,3(2H)-dione (III), containing the (2S)- isomer (Illb), with N,N-carbonyldiimidazole in tetrahydrofuran, preferably without the presence of the catalyst 4-dimethylaminopyridine, said reaction being carried out in such a manner that it is terminated at a moment when the reaction mixture still contains the unreacted compound of formula III in an amount which is in the range of a 3 to 5 fold the initial amount of the (2S)- isomer in the starting substance of formula III.

Classes IPC  ?

• C07D 413/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
• C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles

Abrégé

The invention deals with a preparation method of salts of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (tizanidine) of formula I, especially tizanidine hydrochloride, comprising preparation of a salt of tizanidine of formula I and a carboxylic acid as an intermediate, from which, after acidification with hydrogen chloride, tizanidine hydrochloride is obtained in a high yield and purity.

Classes IPC  ?

• C07D 285/06 - Thiadiazoles-1, 2, 3Thiadiazoles-1, 2, 3 hydrogénés

Abrégé

The invention deals with a preparation method of salts of 5-chloro-4-(2-imidazolin-2-yl- amino)-2,l,3-benzothiadiazole (tizanidine) of formula I, especially tizanidine hydrochloride, comprising preparation of a salt of tizanidine of formula I and a carboxylic acid as an intermediate, from which, after acidification with hydrogen chloride, tizanidine hydrochloride is obtained in a high yield and purity.

Classes IPC  ?

• C07D 417/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre et d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons

Abrégé

A method of preparation of N-(1-benzo[b]thien-2-ylethyl)-N-hydroxyurea of formula (I) with the use of a reaction of l-(benzo[b]thien-2-yl)-ethanol of formula (II) with hydroxyurea of formula (III) in organic solvents, organic acids, their mixtures or in mixtures thereof with water, being catalyzed by strongly acidic cation exchangers or various hydrogen sulphates.

Classes IPC  ?

• C07D 333/56 - Radicaux substitués par des atomes d'oxygène
• C07D 333/58 - Radicaux substitués par des atomes d'azote

Abrégé

A method for preparing 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid of formula (I) by reaction of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one of formula (II) with 4-hydrazinobenzoic acid of formula (III) in an organic acid or in a mixture of an organic acid and an organic solvent.

Classes IPC  ?

• C07D 249/08 - Triazoles-1, 2, 4Triazoles-1, 2, 4 hydrogénés
• C07D 265/22 - Atomes d'oxygène

Abrégé

A method for the preparation of salts of 2-[2-(4-dibenzo[b,fj[l,4]thiazepin-11-yl-1- piperazinyl)ethoxy]ethanol (quetiapine) from the quetiapine base and the respective acid, wherein the salt is precipitated from a mixture of solvents, the mixture being either a mixture of an aromatic hydrocarbon and a ketone or ester, or that of an aromatic hydrocarbon, water and a ketone or ester. The salts of quetiapine are purified by partial crystallization, wherein only a part of the salt of quetiapine is dissolved in a C1 to C6 alcohol used.

Classes IPC  ?

• C07D 281/16 - Cycles à sept chaînons comportant les hétéro-atomes en positions 1, 4 condensés avec des carbocycles ou avec des systèmes carbocycliques condensés avec deux cycles à six chaînons condensés en [b, f]