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【结 构 式】 
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【药物名称】Piretanide, Hoe-118, Eurelix, Tauliz, Arelix 【化学名称】4-Phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoic acid 【CA登记号】55837-27-9 【 分 子 式 】C17H18N2O5S 【 分 子 量 】362.40741 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Diuretics, Loop Diuretics, RENAL-UROLOGIC DRUGS |
合成路线1
The esterification of 4-phenoxy-3-nitro-5-sulfamoylbenzoic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which is reduced with H2 over Raney-Ni in methanol yielding methyl 4-phenoxy-3-amino-5-sulfamoylbenzoate (III). The condensation of (III) with succinic anhydride (B) or succinoyl chloride (A) by means of pyridine in refluxing dioxane affords methyl 4-phenoxy-3N-succinimido-5-sulfamoylbenzoate (IV), which is reduced with borontrifluoride ethearate and NaBH4 in diglyme giving methyl 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoylbenzoate (V). Finally, this compound is hydrolyzed with NaOH in water.
| 【1】 Merkel, W.; et al.; Piretanide (Hoe 118) a new high ceiling salidiuretic. Eur J Med Chem 1976, 11, 5, 399. |
| 【2】 Bormann, D.; et al.; 5-Sulfamoylbenzoic acid derivatives carrying a heterocyclic substituent. DE 2419970; FR 2324298; GB 1504505; US 4010273 . |
| 【3】 Hillier, K.; Castaner, J.; Piretanide. Drugs Fut 1977, 2, 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 |
|---|---|---|---|---|---|---|
| (B) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |
| (A) | 33879 | succinoyl dichloride | 543-20-4 | C4H4Cl2O2 | 详情 | 详情 |
| (I) | 33876 | 3-(aminosulfonyl)-5-nitro-4-phenoxybenzoic acid | C13H10N2O7S | 详情 | 详情 | |
| (II) | 33877 | methyl 3-(aminosulfonyl)-5-nitro-4-phenoxybenzoate | C14H12N2O7S | 详情 | 详情 | |
| (III) | 33878 | methyl 3-amino-5-(aminosulfonyl)-4-phenoxybenzoate | C14H14N2O5S | 详情 | 详情 | |
| (IV) | 33880 | methyl 3-(aminosulfonyl)-5-(2,5-dioxo-1-pyrrolidinyl)-4-phenoxybenzoate | C18H16N2O7S | 详情 | 详情 | |
| (V) | 33881 | methyl 3-(aminosulfonyl)-4-phenoxy-5-(1-pyrrolidinyl)benzoate | C18H20N2O5S | 详情 | 详情 |