1108745-38-5Relevant academic research and scientific papers
Total Synthesis of Entrectinib with Key Photo-Redox Mediated Cross-Coupling in Flow
Cordell, Morgan J.,Adams, Matt R.,Vincent-Rocan, Jean-Fran?ois,Riley, John G.
supporting information, (2021/12/30)
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
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Paragraph 0202; 0205; 0217; 0218, (2018/10/27)
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
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Paragraph 0115-0120, (2015/02/25)
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.
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
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Page/Page column 11, (2014/01/07)
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
SUBSTITUTED INDAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS
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Page/Page column 75-76, (2009/03/07)
Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.
