1034976-52-7

Upstream product

• 889858-12-2 4-bromo-2-fluoro-benzoic acid tert-butyl ester 
• 38041-19-9 4-aminotetrahydropyran 
• 1034975-61-5 4-(4-methylpiperazin-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzoic acid 
• 1034975-62-6 4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzoic acid trifluoroacetic acid salt 
• 1034975-53-5 tert-butyl 4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzoate 
• 1034975-40-0 tert-butyl 4-(4-methylpiperazin-1-yl)-2-(tetrahydropyran-4-ylamino)benzoate 
• 1034975-35-3 tert‐butyl 2‐amino‐4‐(4‐methylpiperazin‐1‐yl)benzoate 
• 942271-61-6 tert-butyl 4-(4-methylpiperazin-1-yl)-2-nitrobenzoate 
• 942271-60-5 tert-butyl 4-fluoro-2-nitrobenzoate 
• 394-01-4 4-fluoro-2-nitrobenzoic acid 

Downstream Products

• 1034976-18-5 N-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide 
• 1231251-48-1 N-(5-benzyloxy-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzamide 
• 1392151-79-9 N-(5-((3,5-difluorophenyl)thio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide 
• 1392151-70-0 N-(5-(N-(3,5-difluorophenyl)sulfamoyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide 
• 1392151-65-3 N-(5-(3,5-difluorophenylthio)-1-(4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido) benzoyl)-1H-pyrazolo[3,4-b]pyrazine-3-yl)-4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide 
• 1392151-64-2 N-(5-((3,5-difluorophenyl)thio)-1H-pyrazolo[3,4-b]pyrazin-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide 
• 1392150-95-6 N-(5-((3,5-difluorophenyl)thio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(4-methylpiperazin-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide 
• 1108745-38-5 N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide 
• 1392151-83-5 5-((3,5-difluorophenyl)thio)-N-(4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 
• 1108743-60-7 N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide 

Relevant academic research and scientific papers

Total Synthesis of Entrectinib with Key Photo-Redox Mediated Cross-Coupling in Flow

By using photo-redox catalysis in flow the newly marketed drug entrectinib (referred to by the brand name Rozlytrek) was synthesized in 6 linear steps from readily available building blocks under mild conditions. Evaluation of multiple intermediates for their use in the critical C?N amination step in flow led to the finding that more electron deficient aryl-halides achieve higher conversion to the desired product. Data supports that more electron rich aryl-halides undergo a significant amount of hydro-dehalogenation compared to the productive C?N bond formation. Through evaluating various entry points into the synthesis of entrectinib, shorter routes were identified albeit in low yields. The modularity of this route will allow chemists to rapidly synthesize a diverse library of compounds through this route. Via different synthetic intermediates, a scale-up route was discovered for the synthesis of entrectinib using photo-redox in flow in less steps than previously reported, highlighting the utility of flow chemistry in the pharmaceutical industry.

Indazole compound for inhibiting kinase activity as well as composition and application thereof

The invention relates to an indazole compound for inhibiting kinase activity and relates to preparation and application of the indazole compound. Specifically, the invention discloses the indazole compound shown as a formula (I), or crystal forms, prodrugs, pharmaceutically acceptable salts, stereoisomers, tautomers, solvates or pharmaceutical compositions of hydrates of the indazole compound. Thecompound and the composition containing the compound, provided by the invention, have excellent inhibition performance on kinase protein, and also have better pharmacokinetics parameter characteristics at the same time; the medicine concentration of the compound in animals can be improved and the curative effect and safety of the medicine are improved. The formula (I) is shown in the description.

PROCESS FOR THE PREPARATION OF N-[5-(3,5-DIFLUORO-BENZYL)-1H-INDAZOL-3-YL]-4-(4-METHYL-PIPERAZIN-1-YL)-2-(TETRAHYDRO-PYRAN-4-YLAMINO)-BENZAMIDE

The present invention relates to a process for the preparation of N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide. Novel solid forms of this compound, their utility in treating diseases caused by deregulated protein kinase activity and pharmaceutical compositions containing them are also object of the present invention.

Derivatives of azaindoles or diazaindoles for treating pain

The present invention relates to a compound of following formula (I): or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions, such as a mixture of enantiomers, notably a racemic mixture; for use in the treatment of pain.

DERIVATIVES OF AZAINDAZOLE OR DIAZAINDAZOLE TYPE FOR TREATING PAIN

The present invention relates to a compound of following formula (I): or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions, such as a mixture of enantiomers, notably a racemic mixture; for use in the treatment of pain.

Derivatives of azaindazole or diazaindazole type for treating a cancer overexpressing trk

The present invention relates to a compound of following formula (I): or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions, such as a mixture of enantiomers, notably a racemic mixture, as well as pharmaceutical composition comprising such a compound, for use in the treatment of a cancer associated with the overexpression of at least one Trk protein.

PROCESS FOR THE PREPARATION OF N-[5-(3,5-DIFLUORO-BENZYL)-1H-INDAZOL-3-YL]-4-(4-METHYL-PIPERAZIN-1-YL)-2-(TETRAHYDRO-PYRAN-4-YLAMINO)-BENZAMIDE

The present invention relates to a process for the preparation of N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl- piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide. Novel solid forms of this compound, their utility in treating diseases caused by deregulated protein kinase activity and pharmaceutical compositions containing them are also object of the present invention

DERIVATIVES OF AZAINDAZOLE OR DIAZAINDAZOLE TYPE AS MEDICAMENT

The present invention relates to a compound of following formula (I): or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions, such as a mixture of enantiomers, notably a racemic mixture; as well as to the use of same as a drug, notably intended for the treatment of cancer, inflammation and neurodegenerative diseases such as Alzheimer's disease; to the use of same as a kinase inhibitor; to the pharmaceutical compositions comprising same; and to methods for the preparation of same.