【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% |
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. |
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 |