154598-58-0

Usage

Uses

Used in Pharmaceutical Research:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a key intermediate in the synthesis of pharmaceutical compounds for various therapeutic applications. Its unique structure and functional groups make it a promising candidate for the development of new drug candidates.
Used in Organic Synthesis:
In the field of organic synthesis, (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a building block for the creation of complex organic molecules. Its fluorinated nature and unique functional groups can be exploited to synthesize a wide range of biologically active molecules.
Used in Medicinal Chemistry:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a valuable building block in medicinal chemistry due to its stability and resistance to metabolic degradation. This property makes it an attractive candidate for the development of new drugs with improved pharmacokinetic profiles.
Used in Drug Discovery:
In the drug discovery process, (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a starting material for the design and synthesis of novel therapeutic agents. Its unique structure and functional groups can be utilized to explore new chemical space and identify potential drug candidates with improved efficacy and safety profiles.
Used in Chemical Research:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is also used in chemical research to study the reactivity and properties of fluorinated alkyne compounds. This can lead to a better understanding of the fundamental chemistry of these types of molecules and potentially uncover new applications in various fields.

Upstream product

• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 201218-09-9 cyclopropyl acetylenyllithium 
• 192935-82-3 2-cyclopropylethynyl-magnesium bromide 
• 216006-64-3 cyclopropylacetylene magnesium chloride 
• 220961-15-9 iodomagnesium cyclopropylacetylide 
• 6746-94-7 Cyclopropylacetylene 
• 1576-35-8 toluene-4-sulfonic acid hydrazide 
• 209414-26-6 (S)-6-chloro-4-(cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-benzo[d][1,3]oxazine 
• 14267-92-6 1-chloro-4-pentyne 
• 168834-43-3 6-amino-3-chloro-α-cyclopropylethynyl-α-(trifluoromethyl)benzyl alcohol 
• 201218-10-2 4-cyclopropyl-1,1,1-trifluoro-but-3-yn-2-one 
• 18437-66-6 N-(t-butoxycarbonyl)-4-chloroaniline 
• 106-47-8 4-chloro-aniline 
• 201218-07-7 tert-butyl-4-chloro-2-(2,2,2-trifluoroacetyl)phenyl carbamate 

Downstream Products

• 391860-73-4 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 1453095-83-4 3-bromo-6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 1453095-77-6 3,6-dichloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 177530-94-8 (S)-N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)pivalamide 

Relevant academic research and scientific papers

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%.

A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1 =H, R2=cyclopropyl) was obtained with an ee of 99.2%.

Efavirenz synthesis method and method for preparing intermediate of efavirenz

The invention discloses an efavirenz synthesis method and a method for preparing an intermediate of efavirenz. The efavirenz synthesis method comprises the following steps: mixing (2S)-2-(2-amino-5-chlorphenyl)-4-cyclopropyl-1, 1, 1-trifluoromethyl-3-butyne-2-ol, methyl tert-butyl ether and a potassium bicarbonate aqueous solution; adding a triphosgene-containing benzene or triphosgene-containingisopropyl ether solution, and reacting until the raw materials disappear; separating liquid, and washing with edible salt water; drying and concentrating the organic phase to obtain a crude product efavirenz; and recrystallizing to obtain the efavirenz. The yield of the product is improved, so that the cost is greatly reduced, and the market competitiveness is improved.

Method for asymmetric synthesis of anti-Aids drug, namely efavirenz key intermediate

The invention discloses a method for asymmetric synthesis of an anti-Aids drug, namely an efavirenz key intermediate. The method comprises the following steps that in an organic solvent, fluoride, anorganic ligand (9S)-6'-methoxy-deoxidized cinchonine-9-ol and cyclopropyl acetylene are evenly stirred, an organic zinc solution is slowly added at the temperature of 15-25 DEG C, after constant-temperature stirring is conducted for 3-5 hours, tetraisopropyl titanate is added, stirring is continued to be conducted for 2-3 hours, then the temperature is decreased to minus 20 DEG C to 0 DEG C, 5-chloro-2-amino-trifluorobenzophenone is added, a mixture is stirred at the temperature of minus 20 DEG C to 0 DEG C for 5-12 hours, after a reaction is completed, a proton source is added for a quenchingreaction, then a certain amount of activated carbon is added, a mixture is stirred for 0.5 hour and filtered, an organic phase and a water phase are separated in an extraction mode, the organic phaseis washed, dried and subjected to vacuum concentration, and after purification, the efavirenz key intermediate is obtained. The technological process is short, the technological condition is mild, operation is easy, environmental protection is achieved, the cost is low, and the method is suitable for industrial production.

Catalytic Enantioselective Synthesis of Key Propargylic Alcohol Intermediates of the Anti-HIV Drug Efavirenz

The catalytic, enantioselective synthesis of key propargylic alcohol intermediates toward the synthesis of the anti-HIV drug efavirenz is reported. Using a recently reported chiral-at-ruthenium catalyst (J. Am. Chem. Soc. 2017, 139, 4322), catalytic enantioselective alkynylations of 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethanone (99% yield, 95% ee) and 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone (97% yield, 99% ee) are achieved using catalyst loadings of merely 0.2 mol % (ca. 500 TON).

METHOD FOR THE MANUFACTURE OF EFAVIRENZ

This invention relates to a method for the manufacture of optically pure (S)-6- chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1 -benzoxazin- 2-one. Specifically, this invention relates to a flow synthesis method for the manufacture of (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1 -benzoxazin-2-one.

Synthetic method of efavirenz key intermediate

The invention provides a synthetic method of an efavirenz key intermediate. The synthetic method comprises the following steps: carrying out reaction on parachloroaniline and pivaloyl chloride to protect amino to obtain N-(4-chlorphenyl)-2,2-dimethyl propanamide; carrying out Friedel-Crafts acylation reaction on the product and Friedel-Crafts acylation under action of aluminum trichloride to hydrolyze to obtain 4-chloro-2-trifluoroacetyl aniline hydrochloride in an acidic condition; and then carrying out alkalization to obtain 4-chloro-2-trifluoroacetyl aniline, carrying out reaction with cyclopropyl acetylene magnesium chloride in a catalytic system formed by a ligand (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol, and carrying out an asymmetrical self-catalytic reaction to obtain the efavirenz key intermediate. The synthetic method of the efavirenz key intermediate, provided by the invention, is cheap and easily available in raw material, low in toxicity of reagent and mild in reaction condition, amino protection and deprotection are not carried out frequently, the line is concise, the yields of reaction of each step are excellent, and the total yield is high.

Octahedral Ruthenium Complex with Exclusive Metal-Centered Chirality for Highly Effective Asymmetric Catalysis

A novel ruthenium catalyst is introduced which contains solely achiral ligands and acquires its chirality entirely from octahedral centrochirality. The configurationally stable catalyst is demonstrated to catalyze the alkynylation of trifluoromethyl ketones with very high enantioselectivity (up to >99% ee) at low catalyst loadings (down to 0.2 mol%).

Method for asymmetrically synthesizing key intermediate for efavirenz which is anti-AIDS (acquired immune deficiency syndrome) medicine

The invention discloses a method for asymmetrically synthesizing a key intermediate for efavirenz which is an anti-AIDS (acquired immune deficiency syndrome) medicine, and belongs to the field of technologies for synthesizing medicines. The method includes carrying out reaction on 2-methyltetrahydrofuran, alkaline reagents, alcohol compounds, chiral ammonia and alcohol solution and cyclopropyl acetylene; adding 5-chlorine-2-amino trifluorobenzene ketone into reaction products and carrying out addition reaction; terminating the reaction by the aid of reaction termination liquid to obtain the key intermediate which is (S)-2-amino-5-chlorine-alpha-cyclopropyl acetylene-alpha-benzotrifluoride benzyl alcohol for the efavirenz. The method has the advantages that required operation procedures for preparing lithium salt, sodium salt or Grignard reagents for cyclopropyl acetylene during industrial production can be omitted, accordingly, the operation difficulty of the reaction can be lowered to a great extent, the cost for the reaction can be reduced to a great extent, and the method is suitable for industrial production.

Preparation method of efavirenz intermediate

The invention relates to a preparation method of an efavirenz intermediate. The method comprises the following steps of reacting a zinc salt or copper salt with an organic ligand (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol in an organic solvent, adding a cyclopropylene reagent; stirring at a constant temperature for 2h and adding 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoro-ethanone, completing stirring reaction, adding a proton source for quenching reaction and separating an organic phase from an aqueous phase through extraction; and adding an oil phase which is obtained through direct concentration and drying of the organic phase to a solution of tetrahydrofuran and methyl alcohol at a certain ratio, and then adding acetic acid and iron powder, stirring and filtering the obtained mixture through kieselguhr, washing, drying, carrying out vacuum concentration and purifying to obtain an efavirenz key intermediate. The 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoro-ethanone is utilized for participating in reaction, so that the method is short in process, mild in condition, simple in operation, green, environment-friendly and low in cost.