Jiangsu Hengrui Medicine Company Ltd.

Jiangsu Hengrui Co., Ltd.

Guaili Wu

Piaoyang Sun

Xiaohui Gao

Yun Lu

Lingjia Shen

Yongjiang Chen

Zhenjun Qiu

Junlei Jia

Quanliang Zhang

Xi Lu

Yongxing Cao

Changshan Guo

Yunpeng Su

Jun Feng

Qiyun Shao

Yuxia Wu

Lin Bian

Liang Zhong

Bo Yuan

A method for preparing a tyrosine kinase inhibitor and a derivative thereof are described. In particular, the present method has a short synthesis route, low costs, easy operation, and is suitable for large-scale production.

Method for preparing tyrosine kinase inhibitor and derivative thereof

A pharmaceutically acceptable salt as a renal outer medullary potassium channel (ROMK) inhibitor, specifically an L-tartrate and a crystal form I and crystal form II thereof, is described. The pharmaceutically acceptable salt of the ROMK inhibitor, specifically the L-tartrate, has improved bioavailability and stability.

Pharmaceutically acceptable salt as renal outer medullary potassium channel inhibitor

The present invention relates to a method for preparing a tyrosine kinase inhibitor and a derivative thereof. The present method has a short synthesis route, low costs, easy operation, and is suitable for large-scale production.

The present invention relates to a crystalline form of a BTK kinase inhibitor and the preparation method thereof. In particular, the present invention relates to a crystal form I of (R)-4-amino-1-(1-(but-2-ynoyl)pyrrolidin-3-yl)-3-(4-(2,6 -difluorophenoxy)phenyl)-1 H-pyrrolo[2,3-d]pyridazin-7(6H)-one (the compound of formula (I)) and the preparation method thereof. The crystal form I of the compound of formula (I) obtained by the present invention has a good crystalline stability and chemical stability, and the crystallization solvent used has a low toxicity and low residue, thus making it more suitable for use in clinical treatment.

Crystalline form of BTK kinase inhibitor and preparation method thereof

Provided are a sodium salt of a uric acid transporter inhibitor and a crystalline form thereof, In particular, provided are a uric acid transporter (URAT1) inhibitor 1-((6-bromo-quinoline-4-yl)thio)cyclobutyl sodium formate (the compound of formula (I)), a crystal form I, and preparation method thereof. The obtained crystal form I of the compound of formula (I) has a good crystal form stability and chemical stability, and the crystallization solvent used has a low toxicity and low residue, and can be better used in clinical treatment. 

Sodium salt of uric acid transporter inhibitor and crystalline form thereof

Provided are an L-proline complex of a sodium-glucose cotransporter 2 inhibitor, and a monohydrate and a crystal of the L-proline complex. Specifically, provided are 1,6-dehydrated-1-C{4-chloro-3-[(3-fluoro-4-ethoxyphenyl)methyl]phenyl}-5-C-(hydroxymethyl)-&#x3b2;-L-idopyranose L-proline (a compound of formula (I)), a monohydrate and a type A crystal thereof, and a preparation method therefor. The obtained type A crystal of the compound of formula (I) has good chemical stability and crystal stability, and the crystallization solvent used has low toxicity and low residue, so the type A crystal can be better used in clinical treatment. 

L-proline complex of sodium-glucose cotransporter 2 inhibitor, monohydrate and crystal form thereof

Provided are a hydroxyethyl sulfonate of a cyclin-dependent protein kinase inhibitor, a crystalline form thereof and a preparation method therefor. Specifically, 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydroxyethyl sulfonate (compound of formula (I)), a crystal form I thereof and a preparation method therefor are provided. Crystal form I of the compound of formula (I) has good chemical and crystalline stability, low toxicity, and low residual crystallization solvent. The compound of formula (I) and crystal form I thereof can be used in improved clinical therapy. 

Hydroxyethyl sulfonate of cyclin-dependent protein kinase inhibitor, crystalline form thereof and preparation method therefor

A crystal form I of a Janus Kinase (JAK) inhibitor (3aR,5s,6aS)&#x2014;N-(3-methoxyl-1,2,4-thiadiazole-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate of formula (I) is provided. Also provided is a method of preparing the crystal form I of the JAK inhibitor of formula (I). The preparation method includes crystallizing any crystal form or amorphous compound solid of formula (I) in a single organic solvent to obtain the form I crystal. The crystal form I has excellent crystal stability and chemical stability. Additionally, the crystal solvent used to produce the crystal form I has low toxicity and a relatively low content of residual solvent, making the compound better suited for clinical treatment. 

Crystal form of bisulfate of JAK inhibitor and preparation method therefor

A crystalline form of an androgen receptor inhibitor and its preparation method are provided. In particular, provided are crystal form I of (S)-4-(3-(4-(2,3-dihydroxypropoxy)phenyl)-4,4-dimethyl-5-carbonyl-2-thioimidazolin-2-yl)-2-(trifluoromethyl)benzonitrile (a compound of formula (I)) and its preparation method. The method includes (a) adding any crystal form or amorphous form of the compound of formula (I) to an organic solvent to obtain a solution and heating the solution until it is clear, followed by cooling the solution to precipitate a crystal; and (b) filtering, washing, and drying the crystal. The obtained crystal form I of the compound of formula (I) has good chemical stability and crystal form stability, and the crystallization solvent used has low toxicity and residue, and is thus better for use in clinical treatment.

Crystalline form of androgen receptor inhibitor and preparation method thereof

Disclosed are a p-toluenesulfonate of a MEK kinase inhibitor, and a crystal form thereof and a preparation method thereof. Specifically disclosed are a 2-((2-fluorine-4-iodophenyl)amino)-1-methyl-4-((6-methylpyridine-3-group)oxygroup)-6-carbonyl-1,6-dihydropyridine-3-formamide p-toluenesulfonate (a compound represented by formula (I)), a crystal form I, and a preparation method thereof. The obtained crystal form I of the compound of formula (I) has good crystal form stability and chemical stability, and the crystallization solvent used has low toxicity and low residue, and is more suitable for use in clinical treatment. 

P-toluenesulfonate for MEK kinase inhibitor, and crystal form thereof and preparation method therefor

Provided are a hydroxyethyl sulfonate of a cyclin-dependent protein kinase inhibitor, a crystalline form thereof and a preparation method therefor. Specifically, 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperidin-4-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydroxyethyl sulfonate (compound of formula (I)), a crystal form I thereof and a preparation method therefor are provided. Crystal form I of the compound of formula (I) has good chemical and crystalline stability, low toxicity, and low residual crystallization solvent. Therefore, the crystal form I can be used in improved clinical therapy. 

A crystal form of JAK kinase inhibitor bisulfate and a preparation method thereof are provided. In particular, a type II crystal of (3aR,5s,6aS)&#x2014;N-(3-methoxyl-1,2,4-thiadiazole-5-yl)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate and a preparation method thereof are described. The preparation method includes steps of crystallizing any solid crystal form or amorphous compound of formula (I) in a single organic solvent or a mixed organic solvent to obtain a type II crystal form of the compound of formula (I). The type II crystal form of the compound of formula (I) obtained by the described methods has good crystal stability and chemical stability. In addition, the solvent used for crystallization has low toxicity and residue, which is better suited for use in clinical treatment. 

Crystalline form of JAK kinase inhibitor bisulfate and a preparation method thereof

The present invention relates to a bisulfate of a Janus kinase (JAK) inhibitor and a preparation method therefor. More specifically, the present invention relates to a (3aR,5s,6aS)&#x2014;N-(3-methoxyl-1,2,4-thiadiazole-5-group)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-group)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate shown in the formula (I), a preparation method therefor, and an application thereof. The bisulfate shown in the formula (I) can be well suitable as a Janus kinase (JAK) inhibitor in clinical work for treating rheumatism or rheumatoid arthritis. 

Bisulfate of janus kinase (JAK) inhibitor and preparation method therefor

Provided are crystalline Form I of (R,E)-N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl)-3-(1-methylpyrrolidin-2-yl) propenamide dimaleate (called SHR1258 dimaleate for short), preparation methods thereof, and pharmaceutical compositions containing the same. The crystalline Form I of SHR1258 dimaleate has good crystal stability and chemical stability, and can be used in the preparation of medicaments for treating diseases related to EGFR receptor tyrosine kinase or HER-2 receptor tyrosine kinase.

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Jiangsu, China

Guaili Wu