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【结 构 式】

【分子编号】16919

【品名】ethyl 1-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate

【CA登记号】

【 分 子 式 】C26H29N3O3

【 分 子 量 】431.53468

【元素组成】C 72.37% H 6.77% N 9.74% O 11.12%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XVIII)

3) The amidation of 4'-methylbiphenyl-2-carboxylic acid (XIV) with tert-butylamine by means of oxalyl chloride in dichloromethane gives the corresponding tert-butylamide (XV), which is brominated with N-bromosuccinimide (NBS) and benzoyl peroxide in CCl4 yielding 4'-(bromomethyl)-N-(tert-butyl)biphenyl-2-carboxamide (XVI). The condensation of (XVI) with 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester (VI) by means of potassium tert-butoxide in DMA affords 1-[2'-(N-tert-butylcarbamoyl)biphenyl-4-ylmethyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester (XVII), which by reaction with oxalyl chloride in dichloromethane is converted into 1-(2'-cyanobiphenyl-4-ylmethyl)-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester (XVIII). The cyclization of (XVIII) with tributyltin azide in toluene gives 4-(1-hydroxy-1-methylethyl)-2-propyl 1-[2'-(5-tetrazolyl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid ethyl ester (XIX), which is finally tritiated with trityl chloride in pyridine to afford 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2'-[1-(triphenylmethyl)-5-tetrazolyl]biphenyl-4-ylmethyl]imidazole-5-carboxylic acid ethyl ester (VIII), already obtained.

1 Mizuno, M.; Sada, T.; Ikeda, M.; Fukuda, N.; Miyamoto, M.; Yanagisawa, H.; Koike, H.; Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist. Eur J Pharmacol 1992, 285, 181-188.
2 Graul, A.; Leeson, P.; Castañer, J.; CS-866. Drugs Fut 1997, 22, 11, 1205.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 16907 ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate C12H20N2O3 详情 详情
(VIII) 16909 ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate C45H44N6O3 详情 详情
(XIV) 16915 4'-methyl[1,1'-biphenyl]-2-carboxylic acid 7148-03-0 C14H12O2 详情 详情
(XV) 16916 N-(tert-butyl)-4'-methyl[1,1'-biphenyl]-2-carboxamide C18H21NO 详情 详情
(XVI) 16917 4'-(bromomethyl)-N-(tert-butyl)[1,1'-biphenyl]-2-carboxamide C18H20BrNO 详情 详情
(XVII) 16918 ethyl 1-([2'-[(tert-butylamino)carbonyl][1,1'-biphenyl]-4-yl]methyl)-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate C30H39N3O4 详情 详情
(XVIII) 16919 ethyl 1-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate C26H29N3O3 详情 详情
(XIX) 16920 ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate C26H30N6O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

 

1 Hedvati L.Pilarsky G, Shenkar-Garcia N.2006. Process for preparing olmesartan medoxomil at pH higher than 2.5.US 20060148870
2 Hedvati L,Pilarsky G-2006. Prooess for the preparation of olmesartan medoxomiL. W0 2006029056(本专利属于Teva Pharmaceutical Industries Ltd.Israeli Teva Phumaceuticals Usa Inc)
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 16906 diethyl 2-propyl-1H-imidazole-4,5-dicarboxylate C12H18N2O4 详情 详情
(II) 16907 ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate C12H20N2O3 详情 详情
(III) 15332 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl 114772-54-2 C14H10BrN 详情 详情
(IV) 16919 ethyl 1-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate C26H29N3O3 详情 详情
(V) 16920 ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxylate C26H30N6O3 详情 详情
(VI) 66557 1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylic acid 144689-24-7 C24H26N6O3 详情 详情
Extended Information