枸橼酸西地那非及关键中间体合成工艺的改进

The improvement of synthesis process for sildenafil citrate and its key intermediate

目的对枸橼酸西地那非及关键中间体西地那非合成工艺进行优化改进。方法以邻乙氧基苯甲酰氯与4-氨基-1-甲基-3-正丙基-1H-吡唑-5-甲酰胺为起始物料,经缩合、环合、氯磺化、磺酰胺化、成盐等一系列反应,制备枸橼酸西地那非。结果关键中间体西地那非纯度在99.5%以上,杂质D(《欧洲药典》)控制在0.3%以下,其他单杂控制在0.15%以下。结论用精制后西地那非制备出枸橼酸西地那非,纯度在99.8%以上,总收率在45%以上。此工艺成本低,容易操作,且适合工业化生产。

Objective To optimize and improve the synthesis process for sildenafil citrate and its key intermediate sildenafil.Methods The sildenafil citrate was prepared from the raw materials of 2-ethoxybenzoyl chloride and 4-amino-1- methyl-3-n-propyl-5-pyrazolecarboxamide by the reactions of condensation, cyclization,chlorosulfonation, sulfonamide and salt.Results The purity of the key intermediate sildenafil was higher than 99.5%, impurity D（EP） was lower than 0.3% and the unspecified single impurity was lower than 0.15%.Conclusion The purity of the sildenafil citrate was above 99.8% and the total yield was 45%.The process was low cost,easy operate and suitable for industrialized production.