N-(tert-butyl)-4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzenesulfonamide -Drug Synthesis Database

【结构式】

【分子编号】65187

【品名】N-(tert-butyl)-4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzenesulfonamide

【CA登记号】

【分子式】C₂₀H₂₁ClFN₃O₃S

【分子量】437.9222632

【元素组成】C 54.85% H 4.83% Cl 8.1% F 4.34% N 9.6% O 10.96% S 7.32%

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：(VI)

Treatment of 4-(acetylamino)phenylsulfonyl chloride (I) with tert-butylamine yields sulfonamide (II), which on deprotection with potassium hydroxide gives amine (III). Reaction of compound (III) with 4-methoxy-3-fluorobenz-aldehyde gives imine (IV), which is cyclized with tosylmethyl isocyanide to afford imidazole (V). Regioselective chlorination of compound (V) with N-chlorosuccinimide (NCS) to afford the chloroimidazole (VI) and then deprotection of the sulfonamide group of (VI) yields cimicoxib in 40% overall yield.

参考文献中间体

合成目标

【1】 Almansa, C.; Torres, M.C.; Gonzalez, C. (J. Uriach & Cia., SA); Novel imidazoles with anti-inflammatory activity. EP 1122243; JP 2002527508; WO 0023426 .
【2】 Almansa Rosales, C.; Gonzales Gonzales, C. (J. Uriach & Cia., SA); Method of preparing 4-(imidazol-1-yl)benzenesulphonamide derivs.. ES 2184633; WO 0316285 .
【3】 Sorbera, L.A., Ramis, I.; Cimicoxib. Drugs Fut 2004, 29 (4): 325.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	65184	3-fluoro-4-methoxybenzaldehyde	351-54-2	C₈H₇FO₂	详情	详情
(I)	19362	4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride	121-60-8	C₈H₈ClNO₃S	详情	详情
(II)	65182	N-{4-[(tert-butylamino)sulfonyl]phenyl}acetamide		C₁₂H₁₈N₂O₃S	详情	详情
(III)	65183	4-amino-N-(tert-butyl)benzenesulfonamide	209917-48-6	C₁₀H₁₆N₂O₂S	详情	详情
(IV)	65185	N-(tert-butyl)-4-{[(Z)-(3-fluoro-4-methoxyphenyl)methylidene]amino}benzenesulfonamide		C₁₈H₂₁FN₂O₃S	详情	详情
(V)	65186	N-(tert-butyl)-4-[5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzenesulfonamide		C₂₀H₂₂FN₃O₃S	详情	详情
(VI)	65187	N-(tert-butyl)-4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)-1H-imidazol-1-yl]benzenesulfonamide		C₂₀H₂₁ClFN₃O₃S	详情	详情

Extended Information