帕珠沙星的合成

Synthesis of Pazufloxacin

以左旋氧氟沙星中间体 (S) 9,10 二氟 3 甲基 2 ,3 二氢 7 氧代 7H 吡啶并 [1,2 ,3 de][1,4]苯并噁嗪 6 羧酸乙酯为起始原料 ,经过与硼酸反应生成氟喹诺酮硼络合物 ,再进行 10位氰乙基化、环丙基化、氰基水解和改进的Hofmann重排 5步反应得帕珠沙星 ,总收率达 5 2 % .在完成目标产物合成的同时 ,对所使用的合成路线进行了改进 。

s)-10-(1-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2, 3-dihydro-7-H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylicacid was synthesized with commercial available (s)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7-H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic ester through cyanomethylation reaction of fluoroquinolone-boracic complex, cyclopropylation reaction, aminoacylation reaction and improvement Hofmann rearrangement reaction,about 5 steps, in a modified synthetic route and optimized reaction condition (52% overall yield).