Abstract

The invention relates to a preparation method of lifitegrast and intermediate compounds thereof. In particular, the invention relates to a synthesis method of lifitegrast, a key intermediate for synthesizing lifitegrast and solvates thereof, and a method for preparing lifitegrast by hydrolyzing the key intermediate or solvates thereof under alkaline condition.

IPC Classes  ?

• 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

Abstract

The invention relates to a preparation method and application of 5-bromo-2-chloro-benzoic acid as a synthetic raw material of a hypoglycemic agent. Specifically, the 5-bromo-2-chloro-benzoic acid is prepared by taking a 5-bromo-2-aminobenzoic acid derivative as an initial raw material through two steps of reactions of diazotization, chlorination and hydrolysis, and the obtained product has the advantages of few isomer impurities, high reaction yield, good purity, low cost and suitability for industrial production. The invention also relates to the application of the 5-bromo-2-amino-benzoic acid in preparing antidiabetic drugs.

IPC Classes  ?

• C07C 51/377 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groupsPreparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by hydrogenolysis of functional groups
• B01J 23/72 - Copper
• B01J 27/122 - Halides of copper
• C07C 41/01 - Preparation of ethers
• C07C 227/16 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
• C07D 309/10 - Oxygen atoms

Abstract

The present invention relates to intermediate compounds of pilocarpine and a preparation method therefor. In particular, the present invention relates to compounds of formula V and formula I for preparing pilocarpine and a preparation method therefor. In the method, a compound of formula II is used as a raw material, and a compound of formula V is obtained after halogenation hydrolysis, oxidation and substitution reactions; and then the compound of formula V is subjected to a reduction reaction and a ring-forming reaction to obtain the compound of formula I. The preparation method of the present invention has the advantages of mild reaction conditions, a simple reaction process, a high total yield, a high purity, etc., and is very suitable for industrial production.

IPC Classes  ?

• 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
• C07D 307/33 - Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
• A61K 31/415 - 1,2-Diazoles
• A61P 27/02 - Ophthalmic agents

Abstract

The present invention relates to the field of synthesis of drug intermediates, in particular to the field of synthesis of key intermediates for preparing the anti-rheumatoid arthritis drug tofacitinib. Specifically, provided are a 1-benzyl-4-methyl-5-alkoxy-1,2,3,6-tetrahydropyridine compound, a synthetic method thereof, and the use thereof in the preparation of a key intermediate cis-1-benzyl-3-methylamino-4-methylpiperidine of tofacitinib.

IPC Classes  ?

• C07D 211/74 - Oxygen atoms

Abstract

The invention relates to a process for preparing pilocarpine and intermediate compounds therefor. In particular, the present invention relates to key intermediates for the preparation of pilocarpine, i.e., compounds of formula I and formula II, and processes for their preparation. One method is to use malic acid as a raw material, react it with alcohol or sulfate ester first, then react with haloethane, etc. to obtain the compound of formula II, and finally react with a halogenating reagent to obtain the compound of formula I; in the other method, n-butyraldehyde is used as a raw material, and is subjected to condensation reaction, oxidation reaction, esterification reaction and sulfonylation reaction in sequence to obtain the compound of formula II, and finally react with a halogenating reagent to obtain the compound of formula I. The preparation method of the present invention has the advantages of mild reaction conditions, simple reaction process, high overall yield and high purity of the target product, and is therefore very suitable for industrial production. The invention relates to a process for preparing pilocarpine and intermediate compounds therefor. In particular, the present invention relates to key intermediates for the preparation of pilocarpine, i.e., compounds of formula I and formula II, and processes for their preparation. One method is to use malic acid as a raw material, react it with alcohol or sulfate ester first, then react with haloethane, etc. to obtain the compound of formula II, and finally react with a halogenating reagent to obtain the compound of formula I; in the other method, n-butyraldehyde is used as a raw material, and is subjected to condensation reaction, oxidation reaction, esterification reaction and sulfonylation reaction in sequence to obtain the compound of formula II, and finally react with a halogenating reagent to obtain the compound of formula I. The preparation method of the present invention has the advantages of mild reaction conditions, simple reaction process, high overall yield and high purity of the target product, and is therefore very suitable for industrial production.

IPC Classes  ?

• C07C 69/34 - Esters of acyclic saturated polycarboxylic acids having an esterified carboxyl group bound to an acyclic carbon atom
• C07C 69/63 - Halogen-containing esters of saturated acids

Abstract

The present invention relates to preparation methods for pilocarpine and the intermediate compounds thereof. Specifically, the present invention relates to key intermediates, i.e. compounds of formula (I) and formula (II), for preparing pilocarpine and preparation methods therefor. According to one of the methods, malic acid is used as a raw material, reacts with an alcohol or sulfate and then reacts with halogenated ethane, etc., to obtain a compound of formula (II), and finally reacts with a halogenating reagent to obtain a compound of formula (I). According to the other method, n-butyraldehyde is used as a raw material and is subjected to a condensation reaction, an oxidation reaction, an esterification reaction and a sulfonylation reaction in sequence to obtain a compound of formula (II), and finally same reacts with a halogenating reagent to obtain a compound of formula (I). The preparation method of the present invention has the advantages of mild reaction conditions, simple reaction process, high total yield and purity of target products, etc., and is therefore very suitable for industrial production.

IPC Classes  ?

• C07C 309/73 - Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
• 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
• 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
• C07C 303/28 - Preparation of esters or amides of sulfuric acidsPreparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
• C07C 309/66 - Methanesulfonates
• C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
• C07C 67/343 - 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 by increase in the number of carbon atoms
• C07C 67/30 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
• C07C 69/63 - Halogen-containing esters of saturated acids

Abstract

The invention relates to ruxolitinib crystal and a pharmaceutical composition thereof. In particular, the invention provides ruxolitinib dihydrate crystal and a preparation method thereof, and ruxolitinib free base in amorphous form and a preparation method thereof, and a pharmaceutical composition comprising ruxolitinib dihydrate crystal or ruxolitinib free base in amorphous form. The crystal, amorphous form and pharmaceutical composition of the invention have simple preparation method, high product yield, and excellent crystal stability, hygroscopicity and processability, and thus are suitable for industrial production.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

Abstract

A ruxolitinib crystal and a pharmaceutical composition thereof. Specifically, provided are a ruxolitinib dihydrate crystal and a preparation method therefor. Further provided are a ruxolitinib free base in amorphous form and a preparation method therefor, and a pharmaceutical composition comprising the ruxolitinib dihydrate crystal or the ruxolitinib free base in amorphous form. The method for preparing the crystal, the amorphous substance and the pharmaceutical composition thereof is simple, and has a high product yield. In addition, the crystal has an excellent stability, hygroscopicity and processability, thereby being suitable for industrial production.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

The present invention relates to an application of 5-bromo-2-(α-hydroxyamyl) sodium benzoate salt (BZP) in treatment of ischemic cardiovascular and cerebral vascular diseases, in particular to a BZP compound for treatment of ischemic stroke and a treatment method, and more specifically, relates to a treatment solution for treating mild and moderate acute ischemic stroke by using the BZP and a pharmaceutical composition comprising the BZP.

IPC Classes  ?

• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to a preparation method for an intermediate compound acting as a posaconazole synthetic drug, and an intermediate compound prepared thereby. The preparation method for a compound of formula (I) provided by the present invention comprises: using methyl 4-(2,4-difluorophenyl)-4-enopentanoic acid or a reduction product thereof, i.e. 4-(2,4-difluorophenyl)-4-entenal formaldehyde, as a starting material; firstly, reacting same with formaldehyde or paraformaldehyde in the presence of a chiral catalyst; then performing characteristic oxidation, an esterification reaction and a halogenation cyclization reaction thereon; and finally, performing hydrolysis and an acid treatment. The preparation method in the present invention has the advantages of mild reaction conditions, a simple reaction process, a high total yield and high purity of target products, etc., and is suitable for industrial production.

IPC Classes  ?

• C07D 307/24 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• 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
• C07D 319/06 - 1,3-DioxanesHydrogenated 1,3-dioxanes not condensed with other rings
• C07C 67/11 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond being mineral ester groups
• C07C 51/31 - Preparation of carboxylic acids or their salts, halides, or anhydrides by oxidation of cyclic compounds with ring-splitting
• C07C 45/41 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
• C07C 69/732 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
• C07C 59/56 - Unsaturated compounds containing hydroxy or O-metal groups containing halogen
• C07C 49/235 - Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the aromatic rings

Abstract

The present invention relates to a preparation method for miglitol. Specifically, the method of the present invention comprises: using a compound represented by formula VI as a raw material, subjecting the raw material to sulfonylation and then to a substitution reaction with ethanolamine, then removing a protecting group, and finally carrying out hydrogenation and cyclization to prepare miglitol. The method of the present invention has the advantages of simple steps, mild reaction conditions, high total yield, high product purity and the like, and is very suitable for industrial production.

IPC Classes  ?

• C07D 211/46 - Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
• C07H 15/18 - Acyclic radicals, substituted by carbocyclic rings
• C07H 23/00 - Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
• C07H 15/12 - Acyclic radicals, not substituted by cyclic structures attached to a nitrogen atom of a saccharide radical
• C07H 1/00 - Processes for the preparation of sugar derivatives

Abstract

The present invention relates to a method for preparing Asenapine. In particular, the present invention relates to a method for preparing pharmaceutically acceptable Asenapine free base and new crystal form thereof, and also relates to methods for preparing the intermediate compounds used in said method.

IPC Classes  ?

• C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

A method for preparing lifitegrast and an intermediate compound of lifitegrast. Specifically, disclosed are a method for synthesizing lifitegrast, a key intermediate for synthesizing lifitegrast, a solvate of lifitegrast, and a method for preparing lifitegrast by hydrolyzing the solvate under an alkaline condition.

IPC Classes  ?

• 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

Abstract

The present invention relates to a method for preparing 5-bromo-2-chloro-benzoic acid as a raw material in hypoglycemic drug synthesis and the use thereof. Specifically, in the present invention, a 5-bromo-2-aminobenzoic acid derivative is used as a starting raw material, and 5-bromo-2-chloro-benzoic acid is prepared by two steps of diazotization and chlorination and hydrolysis reaction. A resulting product has few isomer impurities, the reaction yield is high, the purity is good, the cost is low, and the present invention is suitable for industrial production. The present invention also relates to the use of 5-bromo-2-amino-benzoic acid in the preparation of anti-diabetic drugs.

IPC Classes  ?

• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 63/70 - Monocarboxylic acids
• C07C 227/18 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
• C07C 229/56 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho- position
• C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds

Abstract

The present invention relates to the field of synthesis of drug intermediates, in particular to the field of synthesis of key intermediates for preparing the anti-rheumatoid arthritis drug tofacitinib. Specifically, provided are a 1-benzyl-4-methyl-5-alkoxy-1,2,3,6-tetrahydropyridine compound, a synthetic method thereof, and the use thereof in the preparation of a key intermediate cis-1-benzyl-3-methylamino-4-methylpiperidine of tofacitinib.

IPC Classes  ?

• C07D 211/74 - Oxygen atoms
• C07D 211/56 - Nitrogen atoms

Abstract

The present invention relates to an application of 5-bromo-2-(α-hydroxyamyl) sodium benzoate salt (BZP) in treatment of ischemic cardiovascular and cerebral vascular diseases, in particular to a BZP compound for treatment of ischemic stroke and a treatment method, and more specifically, relates to a treatment solution for treating mild and moderate acute ischemic stroke by using the BZP and a pharmaceutical composition comprising the BZP.

IPC Classes  ?

• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to a nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof, and a method for preparing the intermediate compound.

IPC Classes  ?

• C07D 311/76 - Benzo [c] pyrans
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
• C07C 41/20 - Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
• 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 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07D 303/22 - Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
• C07D 301/14 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
• C07D 301/19 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic hydroperoxides
• C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
• C07F 7/08 - Compounds having one or more C—Si linkages
• A61P 9/08 - Vasodilators for multiple indications
• A61P 9/12 - Antihypertensives
• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• C07C 43/295 - Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
• C07D 303/36 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms

Abstract

The present invention relates to a method for preparing asenapine. Specifically, the present invention relates to a method for preparing a pharmaceutically acceptable asenapine free base and a crystal form thereof, as well as a method for preparing the intermediate compound used in the method.

IPC Classes  ?

• C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• C07D 207/08 - 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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms

Abstract

The present invention relates to a method for preparing Asenapine. In particular, the present invention relates to a method for preparing pharmaceutically acceptable Asenapine free base and new crystal form thereof, and also relates to methods for preparing the intermediate compounds used in said method.

IPC Classes  ?

• C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

The present invention relates to nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof, and a method for preparing the intermediate compound.

IPC Classes  ?

• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07D 311/76 - Benzo [c] pyrans
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
• C07C 41/20 - Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
• 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 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07D 303/22 - Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
• C07D 301/14 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
• C07D 301/19 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic hydroperoxides
• C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
• C07F 7/08 - Compounds having one or more C—Si linkages
• A61P 9/08 - Vasodilators for multiple indications
• A61P 9/12 - Antihypertensives
• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• C07C 43/295 - Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
• C07D 303/36 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms

Abstract

A method for synthesis of Eliglustat and intermediate compounds thereof. Specifically, a method for synthesis of Eliglustat and pharmaceutically acceptable salts thereof, and further to intermediate compounds used in the method and a preparation method for the intermediate compounds. Compared with an existing synthesis method, the method for synthesis of Eliglustat of the present invention uses novel synthetic intermediates and synthesis steps, features ease of operation, high yield, good purity of intermediates and target products, etc., and facilitates industrial production.

IPC Classes  ?

• C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
• 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
• A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• C07C 231/00 - Preparation of carboxylic acid amides
• C07C 209/26 - Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with hydrogen
• C07D 207/04 - 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 no double bonds between ring members or between ring members and non-ring members
• A61K 31/16 - Amides, e.g. hydroxamic acids
• 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
• C07D 413/06 - 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 carbon chain containing only aliphatic carbon atoms

Abstract

The present invention discloses 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt in different crystal forms and the preparation methods thereof, and belongs to the field of pharmaceutical chemistry. Said different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt include: amorphous 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, crystal form A of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, and crystal form B of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt. The different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt obtained according to the present invention have better stability and water-solubility than the mixed forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, thus is advantageous for pharmaceutical use. Moreover, the different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt possess much better therapeutic effect than 5-bromo-2-(α-hydroxypentyl)benzoic acid potassium salt.

IPC Classes  ?

• C07C 63/70 - Monocarboxylic acids
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part

Abstract

The present invention discloses 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt in different crystal forms and the preparation methods thereof, and belongs to the field of pharmaceutical chemistry. Said different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt include: amorphous 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, crystal form A of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, and crystal form B of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt. The different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt obtained according to the present invention have better stability and water-solubility than the mixed forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, thus is advantageous for pharmaceutical use. Moreover, the different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt possess much better therapeutic effect than 5-bromo-2-(α-hydroxypentyl)benzoic acid potassium salt.

IPC Classes  ?

• C07C 63/70 - Monocarboxylic acids
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part

Abstract

4 alkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted benzyl, preferably isopropyl; and two Ar groups may be the same or different, and are each independently selected from the group consisting of substituted or unsubstituted aryl groups, preferably substituted or unsubstituted phenyl, such as p-methoxyphenyl and the like, wherein the compound is preferably in a solid form.

IPC Classes  ?

• C07D 263/26 - Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
• 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 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
• C07D 413/06 - 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 carbon chain containing only aliphatic carbon atoms
• C07D 407/06 - 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 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to a method for synthesis of Eliglustat and intermediate compounds thereof. Specifically, the present invention relates to the field of synthesis of organic compounds, to a method for synthesis of Eliglustat and pharmaceutically acceptable salts thereof, and further to intermediate compounds used in the method and a preparation method for the intermediate compounds. Compared with an existing synthesis method, the method for synthesis of Eliglustat of the present invention uses novel synthetic intermediates and synthesis steps, features ease of operation, high yield, good purity of intermediates and target products, etc., and facilitates industrial production.

IPC Classes  ?

• C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C07D 413/06 - 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 carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to a process for synthesis of Eliglustat and intermediate compounds thereof. In particular, the present invention relates to a process for synthesis of Eliglustat and pharmaceutically acceptable salts thereof, and relates to the intermediate compounds in the process and a process for preparation of the intermediate compounds.

IPC Classes  ?

• C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
• 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
• 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
• A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• C07C 231/00 - Preparation of carboxylic acid amides
• C07C 209/26 - Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with hydrogen
• C07D 207/04 - 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 no double bonds between ring members or between ring members and non-ring members
• A61K 31/16 - Amides, e.g. hydroxamic acids

Abstract

The present invention relates to nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof, and a method for preparing the intermediate compound.

IPC Classes  ?

• C07D 311/76 - Benzo [c] pyrans
• C07C 43/295 - Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
• C07C 41/20 - Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
• C07C 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
• 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 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07F 7/08 - Compounds having one or more C—Si linkages
• C07D 301/14 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
• C07D 301/19 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic hydroperoxides
• C07D 303/22 - Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
• A61P 9/08 - Vasodilators for multiple indications
• A61P 9/12 - Antihypertensives
• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• C07D 303/36 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms

Abstract

The present invention discloses 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt in different crystal forms and the preparation methods thereof, and belongs to the field of pharmaceutical chemistry. Said different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt include: amorphous 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, crystal form A of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, and crystal form B of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt. The different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt obtained according to the present invention have better stability and water-solubility than the mixed forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, thus is advantageous for pharmaceutical use. Moreover, the different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt possess much better therapeutic effect than 5-bromo-2-(α-hydroxypentyl)benzoic acid potassium salt.

IPC Classes  ?

• C07C 63/70 - Monocarboxylic acids
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part

Abstract

The present invention relates to a compound represented by formula (III), R being selected from C1-C4 alkyls, substituted or unsubstituted phenyl or substituted or unsubstituted benzyl, and being preferably selected from isopropyl; and two Ars capable of being the same or different, respectively and separately selected from substituted or unsubstituted aryl, and being preferably selected from substituted or unsubstituted phenyl, such as methoxyphenyl. The compound is preferably in a solid form.

IPC Classes  ?

• C07D 263/22 - Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
• C07D 263/26 - Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
• C07D 413/06 - 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 carbon chain containing only aliphatic carbon atoms
• C07D 307/24 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 307/12 - Radicals substituted by oxygen 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
• 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

Abstract

The present invention relates to a nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof and method for preparing the intermediate compound.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07D 303/22 - Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
• C07D 301/14 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
• C07D 301/19 - Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic hydroperoxides
• C07F 7/08 - Compounds having one or more C—Si linkages
• C07C 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
• C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
• 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 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07C 41/20 - Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds

Abstract

The present invention discloses 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt in different crystal forms and the preparation methods thereof, and belongs to the field of pharmaceutical chemistry. Said different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt include: amorphous 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, crystal form A of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, and crystal form B of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt. The different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt obtained according to the present invention have better stability and water-solubility than the mixed forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt, thus is advantageous for pharmaceutical use. Moreover, the different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt possess much better therapeutic effect than 5-bromo-2-(α-hydroxypentyl)benzoic acid potassium salt.

IPC Classes  ?

• C07C 63/70 - Monocarboxylic acids
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• C07C 51/60 - Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides into halides with the same carboxylic acid part

Abstract

Disclosed are 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salts in different crystal forms, and a preparation method thereof, relating to the field of medicinal chemistry. The 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salts in different crystal forms comprise: an amorphous 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salt, a 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salt in crystal form A, and a 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salt in crystal form B. The different forms of 5-bromine-2-(α- hydroxypentyl)benzoic acid sodium salts obtained in the present invention have better stability and water solubility than mixed 5-bromine-2-(α- hydroxypentyl)benzoic acid sodium salts, which is conducive to drug use. Meanwhile, the therapeutic effect of the 5-bromine-2-(α-hydroxypentyl)benzoic acid sodium salts in different crystal forms are obviously better than that of the 5-bromine-2-(α-hydroxypentyl) potassium benzoate.

IPC Classes  ?

• C07C 65/03 - Compounds having carboxyl groups bound to carbon atoms of six-membered aromatic rings and containing any of the groups OH, O-metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
• C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid

Abstract

The present invention is related to a synthetic intermediate of entecavir and a method for preparing same, and particularly, related to a synthetic intermediate of Formula II for preparing entecavir, a method for preparing the intermediate, and a method for preparing entecavir by using the intermediate of Formula II, wherein R and R' are defined in the specification.

IPC Classes  ?

• C07C 33/02 - Acyclic alcohols with carbon-to-carbon double bonds
• C07C 29/36 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy groups, e.g. O-metal
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine

Abstract

The present invention relates to a preparation method for a medicine and an intermediate compound thereof, specifically, relates to a preparation method for entecavir, an intermediate compound thereof, and a synthesis method for the intermediate compound.

IPC Classes  ?

• C07D 473/02 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6
• C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
• C07C 41/26 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
• 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 69/78 - Benzoic acid esters
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C07D 473/40 - Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
• C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
• C07D 319/08 - 1,3-DioxanesHydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
• C07D 309/12 - Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers

Abstract

The present invention relates to a preparation method for a medicine and an intermediate compound thereof, specifically, relates to a preparation method for entecavir, an intermediate compound thereof, and a synthesis method for the intermediate compound.

IPC Classes  ?

• C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
• C07D 473/40 - Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
• C07C 43/196 - Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
• C07C 41/26 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
• C07C 69/07 - Formic acid esters of monohydroxylic compounds of unsaturated alcohols
• C07C 67/00 - Preparation of carboxylic acid esters
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages