949014-39-5Relevant academic research and scientific papers
An Improved Synthesis of Elvitegravir
Rádl, Stanislav,Stach, Jan,Pí?a, Ond?ej,Cinibulk, Josef,Havlí?ek, Jaroslav,Zajícová, Markéta,Pekárek, Tomá?
, p. 1738 - 1749 (2016/11/23)
An improved process for the active pharmaceutical ingredient of a new HIV integrase inhibitor elvitegravir (1) has been developed. It starts from commercially available 2,4-dimethoxyacetophenone, which is selectively halogenated into the position 5. The 5-halo acetophenones are condensed with dialkyl carbonates to give the corresponding benzoylacetates. Their treatment with N,N-dimethylformamide dimethyl acetal followed by (S)-valinol then provided the corresponding intermediate benzoyl acrylates. Cyclization to the required 1,4-dihydroquinolin-4-oxo derivatives by aromatic nucleophilic substitution of the 2-methoxy group was achieved by treatment with N,O-bis(trimethylsilyl)-acetamide, which also protected the OH group as the trimethylsilyl derivative. Finally, the Negishi coupling with 2-fluoro-3-chlorobenzylzinc bromide and the following hydrolysis provided elvitegravir (1). The preferred variant, the seven-step procedure starting from 2,4-dimethoxyacetophenone, provides elvitegravir in 29.3% yield.
A NEW PRODUCTION METHOD AND NEW INTERMEDIATES OF SYNTHESIS OF ELVITEGRAVIR
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Page/Page column 14, (2014/05/07)
The present solution relates to an improved production method of elvitegravir of formula I, which is being clinically evaluated for treatment of HIV infection. Elvitegravir of formula I is produced via the intermediate of formula II, the preparation of which is also an object of the present solution.
PROCESS FOR PRODUCTION OF 4-OXOQUINOLINE COMPOUND
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Page/Page column 51, (2009/12/28)
The present invention provides a compound useful as a synthetic intermediate for an anti-HIV agent having an integrase inhibitory activity, a production method thereof, and a production method of an anti-HIV agent using the synthetic intermediate. Specifi
