4'-(bromomethyl)-N-(tert-butyl)[1,1'-biphenyl]-2-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】16917

【品名】4'-(bromomethyl)-N-(tert-butyl)[1,1'-biphenyl]-2-carboxamide

【CA登记号】

【分子式】C₁₈H₂₀BrNO

【分子量】346.26694

【元素组成】C 62.44% H 5.82% Br 23.08% N 4.05% O 4.62%

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：(XVI)

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.

参考文献中间体

合成目标

【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

Extended Information