Synthesis of the related substances of aprepitant
10.13220/j.cnki.jipr.2017.07.008
- VernacularTitle:阿瑞匹坦有关物质的合成
- Author:
yuan Zu WANG
1
,
2
;
101113 北京,北京澳合药物研究院有限公司
;
xia Cai HUO
;
bing Zhi ZHENG
Author Information
1. 100850 北京,军事医学科学院毒物药物研究所
2. 101113 北京,北京澳合药物研究院有限公司
- Keywords:
aprepitant;
related substance;
synthesis
- From:
Journal of International Pharmaceutical Research
2017;44(7):707-713
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize four related substances:1b,1c,1d,and 1e according to the synthetic process of aprepi-tant and its quality standard of USP and EP. Methods The impurities 1b,1c,and 1d were synthesized from 3,5-bis(trifluoromethyl) acetophenone through asymmetrical catalytic reduction reaction,condensation reaction,Grignard reaction ,catalytic hydrogenation and substitution. The impurity 1e was synthesized from(R)-α-methylbenzylamine through 7 reaction steps including esterification,reduc-tion,condensation ect. Results All the four related substances were confirmed by LC-MS and NMR. The results indicated that purity of the product surpassed 95%through HPLC. Conclusion These related substances can be taken as the references for the quality con-trol of aprepitant.
