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【结 构 式】 
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【分子编号】61418 【品名】5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride (Light & heat sensitive); 5-Chlorothiophene-2-sulphonylchloride; 5-Chlorothiophenesulphonyl chloride; 2,3-Dimethylthiophene 【CA登记号】2766-74-7 |
【 分 子 式 】C4H2Cl2O2S2 【 分 子 量 】217.09608 【元素组成】C 22.13% H 0.93% Cl 32.66% O 14.74% S 29.54% |
合成路线1
该中间体在本合成路线中的序号：(XV)Key intermediate (XII) is prepared by chlorosulfonation of 2-chlorothiophene (XIV) with ClSO3H and PCl5 to give 5-chlorothien-2-ylsulfonyl chloride (XV), which by treatment with NH4OH in H2O/THF yields sulfonamide derivative (XVI). Finally, sulfonamide (XVI) is condensed with ethyl chloroformate (XVII) by means of Cs2CO3 in THF .
| 【1】 Scarborough, R.M., Pandey, A., Yiannikouros, G.P., Cruskie, M., White, D.C., Mehrotra, M. (Portola Pharmaceuticals, Inc.). Substituted-(quinazolinyl)phenyl thiophenyl-sulfonylureas, methods for making and intermediates thereof. US 2007208045, WO 2007056167. |
| 【2】 Huang, W., Mehrotra, M., Zhang, X., Cannon, H., Grant, C.M. (Portola Pharmaceuticals, Inc.). [4-(6-Halo-7-substituted-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylureas and forms and methods related thereto. EP 1951254, JP 2009515836, US 2007123547, WO 200705619. |
| 【3】 Sharp, E., Quegan, L.J., Pandey, A., Wang, J., Nieder, M., Huang, W. (Portola Pharmaceuticals, Inc.). [4-(6-Fluoro-7-methylamino-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylurea salts, in different crystalline forms, pharmaceutical compositions thereof. EP 2076510, JP 2010526105, WO 2008137809. |
| 【4】 Sharp, E., Quegan, L.J., Pandey, A., Wang, J., Nieder, M., Huang, W. (Portola Pharmaceuticals, Inc.). [4-(6-Fluoro-7-methylamino-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylurea salts, forms and methods related thereto. US 2009156620, WO 2010054020. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 69097 | ethyl N-(5-chlorothien-2-ylsulfonyl)carbamate;[(5-Chlorothien-2-yl)sulfonyl]carbamic acid ethyl ester;Ethyl[(5-chlorothiophen-2-yl)sulfonyl]carbamate;N-[(5-chloro-2-thienyl)sulfonyl]- | 849793-87-9 | C7H8ClNO4S2 | 详情 | 详情 |
| (XIV) | 69098 | 2-chlorothiophene;2-Thienyl chloride | 96-43-5 | C4H3ClS | 详情 | 详情 |
| (XV) | 61418 | 5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride (Light & heat sensitive); 5-Chlorothiophene-2-sulphonylchloride; 5-Chlorothiophenesulphonyl chloride; 2,3-Dimethylthiophene | 2766-74-7 | C4H2Cl2O2S2 | 详情 | 详情 |
| (XVI) | 69099 | 5-chlorothiophene-2-sulfonamide | C4H4ClNO2S2 | 详情 | 详情 | |
| (XVII) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Acylation of 4-bromo-2-nitroaniline (I) with 5-chlorothiophene-2-sulfonyl chloride (II) in pyridine affords sulfonamide (III). The nitro group of (III) is then reduced to amine (IV) by means of hydrazine hydrate in the presence of Raney nickel. Further acylation of amine (IV) with sulfonyl chloride (II) furnishes the target bis-sulfonamide.
| 【1】 Cockerill, G.S.; et al.; Bis(sulfonamides) as inhibitors of aroB. Unsymmetrical sulfonamide substitution and diamine core SAR. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-739. |
| 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) | 59796 | 4-bromo-2-nitroaniline; 4-bromo-2-nitrophenylamine | C6H5BrN2O2 | 详情 | 详情 | |
| (II) | 61418 | 5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulfonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride; 5-Chlorothiophene-2-sulphonyl chloride (Light & heat sensitive); 5-Chlorothiophene-2-sulphonylchloride; 5-Chlorothiophenesulphonyl chloride; 2,3-Dimethylthiophene | 2766-74-7 | C4H2Cl2O2S2 | 详情 | 详情 |
| (III) | 61419 | N-(4-bromo-2-nitrophenyl)-5-chloro-2-thiophenesulfonamide | C10H6BrClN2O4S2 | 详情 | 详情 | |
| (IV) | 61420 | N-(2-amino-4-bromophenyl)-5-chloro-2-thiophenesulfonamide | C10H8BrClN2O2S2 | 详情 | 详情 |