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【结 构 式】 
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【药物名称】Azosemide, SK 110, PLE 1053, Diart, Luret 【化学名称】2-Chloro-5-(1H-tetrazol-5-yl)-4-(2-thienylmethylamino)benzenesulfonamide 【CA登记号】27589-33-9 【 分 子 式 】C12H11ClN6O2S2 【 分 子 量 】370.84147 |
【开发单位】Roche (Originator), Sanofi-synthélabo (Licensee) 【药理作用】Diuretics, RENAL-UROLOGIC DRUGS |
合成路线1
A new synthetic procedure for azosemide has been reported: The condensation of 2-formylthiophene (I) with 2-chloro-4-amino-5-(5-tetrazolyl)benzenesulfonamide (II) by means of polyphosphoric acid (PPA) in DMSO gives the corresponding Schiff base (III), which is reduced with KBH4 in the same solvent.
| 【1】 Baetz, F.; Lauer, K. (Boehringer Ingelheim GmbH); Process for the production of 5-(4'-chloro-5'-sulfamoyl-2'-thenylamino)phenyltetrazole. DE 3034664; JP 57081485 . |
| 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) | 30732 | 2-thiophenecarbaldehyde; Thiophene-2-carboxaldehyde | 98-03-3 | C5H4OS | 详情 | 详情 |
| (II) | 30733 | 4-amino-2-chloro-5-(1H-1,2,3,4-tetraazol-5-yl)benzenesulfonamide | C7H7ClN6O2S | 详情 | 详情 | |
| (III) | 30734 | 2-chloro-5-(1H-1,2,3,4-tetraazol-5-yl)-4-[[(E)-2-thienylmethylidene]amino]benzenesulfonamide | C12H9ClN6O2S2 | 详情 | 详情 |
合成路线2
The reaction of 2-fluoro-4-chloro-5-sulfamoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which by reaction with aqueous NH3 is transformed into the amide (III). The dehydration of (III) with refluxing POCl3 affords the nitrile (IV), which is then condensed with thenylamine (V) to yield 4-chloro-2-thenylamino-5-sulfamoylbenzonitrile (VI). Finally, this compound is cyclized with sodium azide in DMF at 100 C.
| 【1】 Popelak, A.; et al. (Boehringer Ingelheim GmbH); 5-Phenyltetrazole derivatives. DE 1815922; FR 2026688; GB 1237790; US 3665002 . |
| 【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; Hillier, K.; Azosemide. Drugs Fut 1979, 4, 6, 393. |
| 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) | 33234 | 5-(aminosulfonyl)-4-chloro-2-fluorobenzoic acid | C7H5ClFNO4S | 详情 | 详情 | |
| (II) | 33235 | 5-(aminosulfonyl)-4-chloro-2-fluorobenzoyl chloride | C7H4Cl2FNO3S | 详情 | 详情 | |
| (III) | 33236 | 5-(aminosulfonyl)-4-chloro-2-fluorobenzamide | C7H6ClFN2O3S | 详情 | 详情 | |
| (IV) | 33237 | 2-chloro-5-cyano-4-fluorobenzenesulfonamide | C7H4ClFN2O2S | 详情 | 详情 | |
| (V) | 33238 | 2-thienylmethylamine; 2-thienylmethanamine | 27757-85-3 | C5H7NS | 详情 | 详情 |
| (VI) | 33239 | 2-chloro-5-cyano-4-[(2-thienylmethyl)amino]benzenesulfonamide | C12H10ClN3O2S2 | 详情 | 详情 |