非那雄胺的合成新法

New Synthesis of Finasteride

以孕烯醇酮为原料先制得 3 -羰基 -4 -雄甾烯 -17β-羰酸 ,将其与草酰氯反应 ,无需分离即与叔丁胺反应得 17β-酰胺化合物 ,接着打开 A环 ,再与氨反应闭环得 4-氮杂甾体化合物 ,再经氢化和 1,2 -位脱氢制得非那雄胺。本法无需使用昂贵的 2 ,2′-二吡啶二硫化物 ,更适于工业化生产。反应总收率 16%。

Finasteride was synthesized from pregnenolone by the literature methods to give 3 carbonyl 4 androstene 17β carboxylic acid, which reacted with oxalyl chloride and then with t butyl amine in one pot to yield the 17β carboxamide. A ring cleavage of 17β carboxamide and its subsequent ring closure by ammonia giving 4 aza steroid which was hydrogenated to yield 5α 4 aza steroid. Dehydrogenation of the 1,2 position produced the target compound. The new synthetic route avoids the use of expensive reagent 2,2′ dipyridyl disulfide with an overall yield of 16%.