奥拉帕利有关物质的合成

Synthesis of Related Substances of Olaparib

以4-[3-(哌嗪-1-羰基)苄基]-2H-酞嗪-1-酮为原料,经与2-氟-5-[(4-氧代-3,4-二氢酞嗪-1-基)甲基]苯甲酸缩合,得到有关物质A;以4-[3-(哌嗪-1-羰基)苄基]-2H-酞嗪-1-酮为原料,经与丁酸缩合,得到有关物质B;以苯酞、3-氰基苯甲醛为原料,经亲核取代、氰基水解、肼解、酰胺化反应,得到有关物质C.这3种有关物质的制备方法和反应条件温和,操作简单,纯度高,其化学结构均经LR-EI-MS,^1H-NMR和^(13)C-NMR确证,可以用于奥拉帕利的质量研究和控制.

Related substance A was obtained by condensation of 4-[3-(piperazin-1-carbonyl)benzyl-2H-phthalazin-1-one with 2-fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyllbenzoic acid;related substance B was obtained by condensation of 4-[3-(piperazin-1-carbonyl)benzyll-2H-phthalazin-1-one with butyric acid;related substance C was obtained from phthalide and 3-cyanobenzaldehyde via nucleophilic substitution,cyanohydrolysis,hydrazinolysis and amidation.These related substances were prepared under mild reaction conditions,simple operation and high purity,and their chemical structures were confirmed by LR-EI-MS,^(1)H-NMR and ^(13)C-NMR,which can be used for the quality study and control of olaparib.