1177256-05-1

Basic information

• Product Name: R-Elvitegravir
• Synonyms: R-Elvitegravir;6-[(3-Chloro-2-fluorophenyl)methyl]-1,4-dihydro-1-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-3-quinolinecarboxylic acid
• CAS NO: 1177256-05-1
• Molecular Weight: 447.8838232
• EINECS: -0
• Mol File: 1177256-05-1.mol
• Article Data: 3

Chemical Properties

• Melting Point: 150-151℃
• CAS DataBase Reference: R-Elvitegravir(CAS DataBase Reference)
• NIST Chemistry Reference: R-Elvitegravir(1177256-05-1)
• EPA Substance Registry System: R-Elvitegravir(1177256-05-1)

Safety Data

• Hazardous Substances Data: 1177256-05-1(Hazardous Substances Data)

Upstream product

• 1598387-86-0 methyl 3-(5-bromo-2,4-dimethoxyphenyl)-3-oxopropanoate 
• 85070-47-9 1-(bromomethyl)-3-chloro-2-fluorobenzene 
• 182056-48-0 1-(5-bromo-2,4-dimethoxyphenyl)ethan-1-one 
• 869893-91-4 3-chloro-2-fluorobenzyl zinc bromide 
• 829-20-9 2',4'-dimethoxyacetophenone 
• 1598387-97-3 (R)-methyl 3-(1-hydroxy-3-methylbutan-2-ylamino)-2-(5-bromo-2,4-dimethoxybenzoyl)acrylate 
• 1598387-89-3 methyl 2-(5-bromo-2,4-dimethoxybenzoyl)-3-(dimethylamino)acrylate 
• 1177256-74-4 1-((2R)-1-tert-butyldimethylsilyloxy-3-methylbutan-2-yl)-6-(3-chloro-2-fluorobenzyl)-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 
• 124-41-4 sodium methylate 

Relevant articles and documents

An Improved Synthesis of Elvitegravir

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.

Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors

Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.