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 -Drug Synthesis Database

【结构式】

【分子编号】16920

【品名】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

【CA登记号】

【分子式】C₂₆H₃₀N₆O₃

【分子量】474.56284

【元素组成】C 65.8% H 6.37% N 17.71% O 10.11%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIX)

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

合成路线2

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】 Sebastian S,Gade SR, Mallepalli SR, et aL 2007. Process for preparation of olmesartan medoxomiL. W0 2007047838．(本专利属于Dr Reddy's Laboratories Ltd, India; Dr Reddy's Laboratories, Inc)

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	16905	2-propyl-1H-imidazole-4,5-dicarboxylic acid	C₈H₁₀N₂O₄	详情	详情
(II)	16906	diethyl 2-propyl-1H-imidazole-4,5-dicarboxylate	C₁₂H₁₈N₂O₄	详情	详情
(III)	66559	5-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole	C₁₄H₁₁BrN₄	详情	详情
(IV)	66556	dimethyl 1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-propyl-1H-imidazole-4,5-dicarboxylate	C₂₄H₂₄N₆O₄	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)	16910	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-carboxylic acid	C₄₃H₄₀N₆O₃	详情	详情
(VII)	16911	4-(chloromethyl)-5-methyl-1,3-dioxol-2-one	C₅H₅ClO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【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