391860-73-4

Usage

Uses

Used in Pharmaceutical Industry:
Efavirenz Related Compound C (20 mg) (6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline) is used as an impurity in the production of Efavirenz, a nonnucleoside HIV-1 reverse transcriptase inhibitor and antiviral agent. Its presence in the final product is controlled and monitored to ensure the safety and efficacy of the antiviral medication. Efavirenz Related Compound C (20 mg) (6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline) plays a role in the development and manufacturing process of Efavirenz, contributing to the overall effectiveness of the drug in treating HIV-1 infections.

Upstream product

• 108-90-7 chlorobenzene 
• 209414-27-7 (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol 
• 6746-94-7 Cyclopropylacetylene 
• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 168834-43-3 6-amino-3-chloro-α-cyclopropylethynyl-α-(trifluoromethyl)benzyl alcohol 
• 173676-59-0 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride 
• 765-43-5 Cyclopropyl methyl ketone 
• 209414-26-6 (S)-6-chloro-4-(cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-benzo[d][1,3]oxazine 

Relevant academic research and scientific papers

Synthesis method of efavirenz quinoline impurities

The invention provides a preparation method for simply and efficiently preparing efavirenz quinoline impurities (III). The preparation method comprises the steps of adding (S)-1-(2-amino-5-chlorophenyl)-1-trifluoromethyl-cyclopropyl-2-allylene-ol (II) into an organic solvent and stirring and reacting under the action of a catalyst and an organic acid to obtain the efavirenz quinoline impurities (III). The formula (II) and the formula (III) are shown in the description.

NHC-Cu(I)-Catalyzed Friedl?nder-Type Annulation of Fluorinated o-Aminophenones with Alkynes on Water: Competitive Base-Catalyzed Dibenzo[b,f][1,5]diazocine Formation

An efficient, easily scalable synthesis of 4-trifluoromethylquinolines and naphthydrines (as well as their difluoro- and perfluoro-analogues) as a result of tandem direct catalytic alkynylation/dehydrative condensation of o-aminofluoromethylketones (o-FMKs), for the first time catalyzed by NHC-copper(I) complexes on water, is reported. A wide range of terminal alkynes is tolerated under the reaction conditions, including β-lactam-, steroid-, and sugar-derived ones, leading to desired quinolines and naphthydrines with good yields. Further investigations proved that o-FMKs could be efficiently transformed into a rare class of heterocyclic compounds - dibenzo[b,f][1,5]diazocines - by a base-catalyzed condensation, also on water. The developed method was applied for gram-scale synthesis of a fluorinated analogue of G protein-coupled receptor antagonist (GPR91).

Electrophile-driven copper-catalyzed one-pot synthesis of 3-halogen quinoline derivatives

A convenient and regioselective one-pot synthesis of 3-chloride or 3-bromide quinoline derivatives was achieved through a Grignard addition reaction by alkynyl Grignard regent to o-trifluoroacetyl aniline and a Cu(II)-catalyzed cyclization-halogenation tandem reaction with aqueous HCl or HBr as electrophilic reagent.

Electrophile-driven copper-catalyzed one-pot synthesis of 3-halogen quinoline derivatives

A convenient and regioselective one-pot synthesis of 3-chloride or 3-bromide quinoline derivatives was achieved through a Grignard addition reaction by alkynyl Grignard regent to o-trifluoroacetyl aniline and a Cu(II)-catalyzed cyclization-halogenation tandem reaction with aqueous HCl or HBr as electrophilic reagent.

Silver catalyzed synthesis of 4-trifluoromethyl substituted quinolines in water

Herein we report the first silver catalyzed fluorinated quinoline synthesis via a cascade alkyne-ketone-amino coupling/addition/condensation process in water.

Proline potassium salt: A superior catalyst to synthesize 4-trifluoromethyl quinoline derivatives via Friedlander annulation

Proline potassium salt was successfully firstly used to catalyze the Friedlander annulation toward the synthesis of 4-trifluoromethyl-substituted quinolines from the substituted 2-trifluoroacetyl anilines and variety carbonyl compounds under mild conditions in good to excellent yields. This catalyst provides several advantages, such as shorter reaction time, high regioselectivity, functional group tolerance, and broad substrate scope.

Zinc(II) iodide-triethylsilane: A novel mild reduction system for direct deoxygenation of aryl aldehydes, ketones, and α,β-unsaturated enones

ZnI2-TESH has been found to be a novel mild and efficient reduction system. This reagent, in contrast to the traditional ionic deoxygenation systems (TFA-R3SiH, BF3·OEt 2-R3SiH, etc.), could directly deoxygenate different kinds of carbonyl compounds such as aryl aldehydes, ketones, and αβ- unsaturated enones to the corresponding hydrocarbons in moderate to excellent yields. Georg Thieme Verlag Stuttgart.

The first proline-catalyzed Friedlander annulation: Regioselective synthesis of 2-substituted quinoline derivatives

The first proline-catalyzed Friedlander annulation for the synthesis of 2-substituted 4-trifluoromethyl quinoline derivatives is described. Excellent regioselectivity as well as good yields were shown in a variety of cases, and a tandem aldolcyclization pathway might be involved. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Zn(II)-mediated alkynylation-cyclization of o-trifluoroacetyl anilines: One-pot synthesis of 4-trifluoromethyl-substituted quinoline derivatives

A novel efficient route to 4-trifluoromethylsubstituted quinoline derivatives through the Zn(II)-mediated alkynylation-cyclization of o-trifluoroacetyl anilines is described.

Oxidative removal of p-methoxybenzyl-amino protecting group in the presence of a proximal hydroxy function: A solution to a process problem in SUSTIVA (efavirenz) synthesis

A practical and scaleable synthetic procedure for the deprotection of a p-methoxy benzyl group from the tertiary carbinol 2 in the commercial synthesis of SUSTIVA (efavirenz) 1 is described. The methodology involves a two step, one pot operation with an isolated yield of 82.5% with a product purity of >99.5%.