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【结 构 式】 
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【分子编号】44347 【品名】2-hydroxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoic acid 【CA登记号】 |
【 分 子 式 】C12H16N2O5S 【 分 子 量 】300.33552 【元素组成】C 47.99% H 5.37% N 9.33% O 26.64% S 10.68% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Synthesis of sildenafil: Reaction of 5-(chlorosulfonyl)-2-hydroxybenzoic acid (XIV) with 1-methylpiperazine (XV) by means of DIEA gives the sulfonamide (XVI), which is treated with diethyl sulfate yielding 2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)benzoic acid (XVII). The activation of (XVII) with a polymer-supported 1-hydroxybenzotriazole (HOBt) variant (XVIII) and bromotris(pyrrolidino)phosphonium (PyBrOP) as catalyst affords the activated ester (XIX), which is condensed with the aminopyrazole intermediate (XIII), and treated with the methyl isocyanate resin (X) in order to eliminate the excess of aminopyrazole (XIII), to provide the diamide (XX). Finally, the cyclization and dehydration to sildenafil are performed by microwave irradiation of an ethanolic solution of compound (XX) containig a catalytic amount of NaOEt.
| 【1】 Baxendale, I.R.; Ley, S.V.; Polymer-supported reagents for multi-step organic synthesis: Application to the synthesis of sildenafil. Bioorg Med Chem Lett 2000, 10, 17, 1983. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 11019 | (Methylimino)(oxo)methane; methyl isocyanate | C2H3NO | 详情 | 详情 | |
| (XIII) | 15627 | 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide; 4-amino-1-methyl-3-propyl-5-pyrazolecarboxamide | 139756-02-8 | C8H14N4O | 详情 | 详情 |
| (XIV) | 44346 | 5-(chlorosulfonyl)-2-hydroxybenzoic acid | C7H5ClO5S | 详情 | 详情 | |
| (XV) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (XVI) | 44347 | 2-hydroxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoic acid | C12H16N2O5S | 详情 | 详情 | |
| (XVII) | 21188 | 2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoic acid | 194602-23-8 | C14H20N2O5S | 详情 | 详情 |
| (XVIII) | 44348 | 1-hydroxy-1H-1,2,3-benzotriazole-6-carbaldehyde | C7H5N3O2 | 详情 | 详情 | |
| (XIX) | 44349 | 1-([2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoyl]oxy)-1H-1,2,3-benzotriazole-6-carbaldehyde | C21H23N5O6S | 详情 | 详情 | |
| (XX) | 21191 | 4-([2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoyl]amino)-1-methyl-3-propyl-1H-pyrazole-5-carboxamide | C22H32N6O5S | 详情 | 详情 |