302964-20-1

Basic information

• Product Name: Carbamic acid, [5-(chlorocarbonyl)-2-thiazolyl]-, 1,1-dimethylethyl ester (9CI)
• Synonyms: Carbamic acid, [5-(chlorocarbonyl)-2-thiazolyl]-, 1,1-dimethylethyl ester (9CI)
• CAS NO: 302964-20-1
• Molecular Formula: C₉H₁₁ClN₂O₃S
• Molecular Weight: 262.71
• Mol File: 302964-20-1.mol

Chemical Properties

• Appearance: /
• Density: 1.400±0.06 g/cm3(Predicted)
• PKA: 4.75±0.70(Predicted)
• CAS DataBase Reference: Carbamic acid, [5-(chlorocarbonyl)-2-thiazolyl]-, 1,1-dimethylethyl ester (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Carbamic acid, [5-(chlorocarbonyl)-2-thiazolyl]-, 1,1-dimethylethyl ester (9CI)(302964-20-1)
• EPA Substance Registry System: Carbamic acid, [5-(chlorocarbonyl)-2-thiazolyl]-, 1,1-dimethylethyl ester (9CI)(302964-20-1)

Safety Data

• Hazardous Substances Data: 302964-20-1(Hazardous Substances Data)

Upstream product

• 302964-01-8 ethyl 2-[(tert-butoxycarbonyl)amino]-1.3-thiazole-5-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 302964-02-9 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylic acid 

Downstream Products

• 1444001-05-1 (S)-ethyl 1-(4-(5-((2-((tert-butoxycarbonyl)amino)thiazole-5-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)piperidine-4-carboxylate 
• 1444001-42-6 ethyl 1-(4-((S)-5-((2-((tert-butoxycarbonyl)amino)thiazole-5-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)-3-methyl-2-oxopiperidine-3-carboxylate 
• 1444001-41-5 ethyl 1-(4-((S)-5-((2-((tert-butoxycarbonyl)amino)thiazole-5-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)-2-oxopiperidine-4-carboxylate 
• 1444001-40-4 ethyl 1-(4-((S)-5-((2-((tert-butoxycarbonyl)amino)thiazole-5-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)piperidine-2-carboxylate 
• 302964-06-3 [5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl]-carbamic acid tert-butyl ester 
• 302957-97-7 [5-[[(2,4,6-trimethylphenyl)amino]carbonyl]-2-thiazolyl]carbamic acid-1,1-dimethylethyl ester 
• 934193-04-1 [5-[[(2,6-dimethylphenyl)amino]carbonyl]-2-thiazolyl]carbamic acid 1,1-dimethylethyl ester 

Relevant articles and documents

Scalable and impurity-free process for dasatinib: Src and BCR-Abl inhibitor

An efficient, telescopic, impurity-free and scalable process for Bcr-Abl and Src family tyrosine kinase inhibitor for synthesis of Dasatinib with high yield and purity is described.

AN IMPROVED PROCESS FOR THE PREPARATION OF DASATINIB POLYMORPH

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A convenient new and efficient commercial synthetic route for dasatinib (Sprycel)

A new and efficient synthetic route for dual-Src/Abl kinase inhibitor dasatinib (Sprycel), an anticancer drug, is described. This commercially viable process yields dasatinib monohydrate free of potential impurities with consistent yield of 68% in route A and 61% in route B with HPLC purity >99.80% over four stages.

EMS ANALOGUES OF LYN/SRC-TYROSINE KINASE INHIBITORS

Embodiments of the present invention are directed to compounds of the formula API―LG―ESM wherein "API" is a monovalent substituent group of an enzyme inhibitor; "LG" is a divalent substituent group of a linking group; and "ESM" is a monovalent substituent group of an esterase sensitive motif; or a pharmaceutically acceptable salt thereof. Other embodiments are directed to methods for using compounds of the formula API―LG―ESM to treat a number of medical conditions, including Alzheimer's disease.

PYRIDINONE AND PYRIMIDINONE DERIVATIVES AS FACTOR XIA INHIBITORS

The present invention provides compounds of the general formula (I), their salts and N- oxides, and solvates and prodrugs thereof (wherein the characters are as defined in the description). The compounds of the general formula (I) are inhibitors of Factor XIa, so that they are useful in the prevention of and/or therapy for thromboembolic diseases.

A new and efficient preparation of 2-aminothiazole-5-carbamides: Applications to the synthesis of the anti-cancer drug dasatinib

A new and efficient method has been developed for the synthesis of 2-amino-N-(-(2-chloro-6-methylphenyl)-thiazole-5-carboxamide. The new method involves a chemoselective α-bromination of β-ethoxyacrylamide followed by a one-pot treatment with thiourea to give the desired 2-aminothiazole-5-carboxylamide in excellent yield. Application of this new method to the efficient synthesis of the anti-cancer drug dasatinib was demonstrated.

2-Aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6- [4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-1, 3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor

2-Aminothiazole (1) was discovered as a novel Src family kinase inhibitor template through screening of our internal compound collection. Optimization through successive structure-activity relationship iterations identified analogs 2 (Dasatinib, BMS-354825) and 12m as pan-Src inhibitors with nanomolar to subnanomolar potencies in biochemical and cellular assays. Molecular modeling was used to construct a putative binding model for Lck inhibition by this class of compounds. The framework of key hydrogen-bond interactions proposed by this model was in agreement with the subsequent, published crystal structure of 2 bound to structurally similar Abl kinase. The oral efficacy of this class of inhibitors was demonstrated with 12m in inhibiting the proinflammatory cytokine IL-2 ex vivo in mice (ED50 ～ 5 mg/kg) and in reducing TNF levels in an acute murine model of inflammation (90% inhibition in LPS-induced TNFα production when dosed orally at 60 mg/kg, 2 h prior to LPS administration). The oral efficacy of 12m was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally at 0.3 and 3 mg/kg twice daily. Dasatinib (2) is currently in clinical trials for the treatment of chronic myelogenous leukemia.

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Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56Lck inhibitors

A series of substituted 2-(aminoheteroaryl)-thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy. A series of substituted 2-(aminoheteroaryl)- thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy.

Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinase p56Lck

A novel series of 2-amino-5-carboxamidothiazoles were identified as inhibitors of Lck. Structure-activity studies demonstrate the structural requirements for potent Lck activity. Cyclopropylamide 11d is a potent Lck inhibitor having sub-micromolar activity in a PBL proliferation assay.