(E)-3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylic acid -Drug Synthesis Database

【结构式】

【分子编号】67770

【品名】(E)-3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylic acid

【CA登记号】　

【分子式】C₃₄H₃₃BrN₆O₃

【分子量】653.579

【元素组成】C 62.48% H 5.09% Br 12.23% N 12.86% O 7.34%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

Chlorination of carboxylic acid (I) with SOCl2 in the presence of NMP in THF/toluene, followed by condensation of the resulting acid chloride with the amine HCl (II) or its free base using DIEA in THF, provides the carboxamide (IVa) . Alternatively, condensation of carboxylic acid (I) with the amino esters (IIIa) or (IIIb) by means of HATU and Et3N or DIEA in DMSO affords the corresponding carboxamides (IVb) or (IVc) . Finally, butyl (IVa) ,methyl (IVb) or ethyl (IVc) esters are hydrolyzed with aqueous NaOH in THF/MeOH at 67 °C or DMSO , and then treated with aqueous NaOH in THF .

参考文献中间体

合成目标

【1】 Boecher, W., Haefner, C., Kukolj, G. (Boehringer Ingelheim Pharma GmbH & Co. KG). Combination therapy for treating HCV infection. CN 103228278, EP 2621495, JP 2013540112, KR 2013116245, US 2012135949, WO 2012041771.
【2】 Brickl, R.-S., Chen, S., Chung, J. et al. (Boehringer Ingelheim Pharma GmbH & Co. KG). Solid state forms of a potent HCV inhibitor. CN 103153987, EP 2621921, JP 2013543495, KR 2013108326, US 2012122887, US 8598183, US 2014057928, WO 2012044520. 3. Mensa, F., Nehmiz, G. (Boehringer Ingelheim Pharma GmbH & Co. KG). Oral combination therapy for treating HCV infection in specific patient subgenotype populations. WO 2013147749.
【3】 Mensa, F. (Boehringer Ingelheim Pharma GmbH & Co. KG). Oral combination therapy for treating HCV infection in specific patient sub-population. WO 2013147750.
【4】 LaPlante, S.R., Boes, M., Brochu, C. et al. Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors. Discovery of deleobuvir (BI 207127). J Med Chem 2014, 57(5): 1845-54.
【5】 Mensa, F., Nehmiz, G. (Boehringer Ingelheim Pharma GmbH & Co. KG). Oral combination therapy for treating HCV infection in specific patient subgenotype populations. WO 2013147749.
【6】 Tsantrizos, Y.S., Chabot, C., Beaulieu, P. et al. (Boehringer Ingelheim Pharma GmbH & Co. KG). Viral polymerase inhibitors. CN 102911161, CN 103304541, CN 103319464, CN 103333162, EP 1718608, EP 2626354, JP 2007523094, JP 2010195818, JP 2010280740, KR 2012091276, US 2005222236, US 8030309, WO 2005080388.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IIIa)	67765	(E)-methyl 3-(2-(1-aminocyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate	C₁₆H₁₉N₃O₂	详情	详情
(IIIb)	67766	(E)-ethyl 3-(2-(1-aminocyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate	C₁₇H₂₁N₃O₂	详情	详情
(IVa)	67769	(E)-butyl 3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate	C₃₈H₄₁BrN₆O₃	详情	详情
(IVb)	67768	(E)-methyl 3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate	C₃₅H₃₅BrN₆O₃	详情	详情
(IVc)	67767	(E)-ethyl 3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate	C₃₆H₃₇BrN₆O₃	详情	详情
(I)	67763	2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylic acid	C₁₉H₁₈BrN₃O₂	详情	详情
(II)	67764	(E)-butyl 3-(2-(1-aminocyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylate dihydrochloride	C₁₉H₂₅N₃O₂.2HCl	详情	详情
(V)	67770	(E)-3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylic acid	C₃₄H₃₃BrN₆O₃	详情	详情

Extended Information