Improved synthesis of raltegravir
10.3321/j.issn:1000-5048.2009.04.002
- VernacularTitle:Raltegravir的合成工艺研究
- Author:
Diliang GUO
;
Guannan LIU
;
Jian LI
;
Yu ZHOU
;
Jinyi XU
;
Hualiang JIANG
;
Hong LIU
- Publication Type:Journal Article
- Keywords:
HIV-1 integrase;
raltegravir;
synthesis;
process research
- From:
Journal of China Pharmaceutical University
2009;40(4):297-301
- CountryChina
- Language:Chinese
-
Abstract:
Aim: To develop a practical synthetic route of raltegravir, a drug for HIV treatment. Methods: Raltegravir was synthesized through an eight-step process including aminonitrile formation, protection with benzyloxy-carbonyl group, conversion of the nitrile to the amidoxime, cyclization to form hydroxypyrimidinone, N-methyla-tion, amidation with microwave-assistance, deprotection, amidation with acyl chloride. Results: The overall yield of the eight-step synthesis is about 12. 0% and the structure of the target compound was confirmed by ~1H NMR, ~(13)C NMR, LR-MS and HR-MS. Conclusion: The reported synthetic process of raltegravir highlights the advantages in terms of readily available starting materials, convenient operation and low cost.
