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【结 构 式】

【分子编号】19362

【品名】4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride

【CA登记号】121-60-8

【 分 子 式 】C8H8ClNO3S

【 分 子 量 】233.67516

【元素组成】C 41.12% H 3.45% Cl 15.17% N 5.99% O 20.54% S 13.72%

与该中间体有关的原料药合成路线共 4 条

合成路线1

该中间体在本合成路线中的序号:(VII)

2) The reaction of fluorobenzene (VI) with N-acetylsulfanilyl chloride (VII) in the presence of anhydrous aluminum chloride gives the desired acetamide in one step.

1 Durr, F.E.; Lang, S.A. Jr.; Shang Wang, B.; Ruszala-Mallon, V.; Lin, Y.-i.; Fields, T.L.; CL-259,763. Drugs Fut 1987, 12, 5, 431.
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) 17466 Fluorobenzene 462-06-6 C6H5F 详情 详情
(VII) 19362 4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride 121-60-8 C8H8ClNO3S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(A)

Beckmann rearrangement of oxime (I) in the presence of p-acetamidobenzenesulfonyl chloride and pyridine afforded acetamide (II). Subsequent fluorination of (II) using perchloryl fluoride produced fluoroenamide (III), which was hydrolyzed with HCl to give fluoroketone (IV). After treatmentof (IV) with o-phenylenephosphorochloridite (V) and pyridine, the intermediate phosphite ester (VI) was converted to iodide (VII) by means of iodine in CH2Cl2. Finally, reductive deiodination of (VI) with Zn in AcOH produced the target compound.

1 Lewbart, M.L.; Schwartz, A.G. (Research Corporation Technologies, Inc.); Steroids useful as anti-cancer and anti-obesity agents, a therapeutic compsn. containing them and use thereof for the preparation of a therapeutic compsn.. EP 0246650; JP 1987283993 .
2 Schwartz, A.G.; Lewbart, M.L.; 17-Hydroxy-steroids. US 4898694 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 19362 4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride 121-60-8 C8H8ClNO3S 详情 详情
(I) 30068 (3S,8R,9S,10R,13S,14S)-17-ethanimidoyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate C23H33NO3 详情 详情
(II) 30069 (3S,8R,9S,10R,13S,14S)-17-(acetamido)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate C23H33NO3 详情 详情
(III) 30070 (3S,8R,9S,10R,13S,14S)-17-(acetamido)-16-fluoro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate C23H32FNO3 详情 详情
(IV) 30071 (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one C19H27FO2 详情 详情
(V) 30072 2-chloro-1,3,2-benzodioxaphosphole 1641-40-3 C6H4ClO2P 详情 详情
(VI) 30073 (3S,8R,9S,10R,13S,14S,16R)-3-(1,3,2-benzodioxaphosphol-2-yloxy)-16-fluoro-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one C25H30FO4P 详情 详情
(VII) 30074 (3S,8R,9S,10R,13S,14S,16R)-16-fluoro-3-iodo-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one C19H26FIO 详情 详情

合成路线3

该中间体在本合成路线中的序号:(I)

Condensation of 4-acetamidobenzenesulfonyl chloride (I) with 4-amino-2,6-dibromopyridine (II) in pyridine at 60 C afforded sulfonamide (III). The acetamido group was then hydrolyzed in refluxing 1 N NaOH to give (IV). Finally, substitution of both bromine atoms for methylamino groups was carried out by heating with liquid MeNH2 at 160 C in an autoclave.

1 Wagner, A.; Heitsch, H.; Nolkne, G.; Wirth, K.; Bernard, P. (Aventis SA); Fluoralkyl- and fluoralkoxy-substd. heterocyclic bradykinin antagonists. EP 0796848; JP 1998007656; US 5859025 .
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) 19362 4-(acetamido)benzenesulfonyl chloride; N-acetylsulfanilyl chloride 121-60-8 C8H8ClNO3S 详情 详情
(II) 19363 2,6-dibromo-4-pyridinamine; 2,6-dibromo-4-pyridinylamine C5H4Br2N2 详情 详情
(III) 19364 N-(4-[[(2,6-dibromo-4-pyridinyl)amino]sulfonyl]phenyl)acetamide C13H11Br2N3O3S 详情 详情
(IV) 19365 4-amino-N-(2,6-dibromo-4-pyridinyl)benzenesulfonamide C11H9Br2N3O2S 详情 详情

合成路线4

该中间体在本合成路线中的序号:(I)

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.

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