Synthetic process improvement of raltegravir / 国际药学研究杂志
Journal of International Pharmaceutical Research
;
(6): 595-599, 2017.
Article
in Chinese
| WPRIM
| ID: wpr-617575
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).
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Journal of International Pharmaceutical Research
Year:
2017
Type:
Article
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