Synthetic process improvement of raltegravir
10.13220/j.cnki.jipr.2017.06.024
- VernacularTitle:拉替拉韦的合成工艺改进
- Author:
Daoxu ZHANG
;
Chao LI
- Keywords:
HIV integrase inhibitor;
raltegravir;
process improvement
- From:
Journal of International Pharmaceutical Research
2017;44(6):595-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective To improve the synthetic procedure of the HIV integrase inhibitor raltegravir. Methods With 2-ami-no-2-methyl-propionitrile hydrochloride as starting material,the target compound raltegravir was synthesized through amino protection by benzyl chloroformate ,amidoxime formation,cyclization induced by michael addition&Claisen rearrangement,N-methylation,N-acylation,hydroxyl protection by trimethylacetyl chloride,hydrogenolysis by the system of Pd/C and formic acid,amidation with the 5-methyl-1,3,4-oxadiazol-formyl chloride,and immediate hydrolysis without more purification. Results The chemical structure of raltegravir and the intermediates were characterized by 1H NMR,13C NMR and MS. The overall yield was about 19.45%. Conclusion Compared with the preceding process,the developed route is easy to operate,safe and suitable for industrialized production in accor-dance with the quality standard of active pharmaceutical ingredient(API).
