241479-74-3

Basic information

• Product Name: (αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile
• Synonyms: (αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile;Isavuconazole interMediate 7;241479-74-3 (2S,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-Methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile;(alphaS,betaR)-beta-(2,5-Difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanenitrile;(2s,3r)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1h-1,2,4-triazol-1-yl)butanenitrile;Isavuconazole intermediate;(2S,3R)-3-(2,5-Difluorophenyl)-3-hydroxy-2-Methyl-1H-1,2,4-triazole-1-butanenitrile;1H-1,2,4-Triazole-1-butanenitrile, β-(2,5-difluorophenyl)-β-hydroxy-α-methyl-, (αS,βR)-
• CAS NO: 241479-74-3
• Molecular Formula: C₁₃H₁₂F₂N₄O
• Molecular Weight: 278.2573864
• EINECS: 1592732-453-0
• Mol File: 241479-74-3.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 522.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.32±0.1 g/cm3(Predicted)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 10.95±0.29(Predicted)
• CAS DataBase Reference: (αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile(CAS DataBase Reference)
• NIST Chemistry Reference: (αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile(241479-74-3)
• EPA Substance Registry System: (αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile(241479-74-3)

Safety Data

• Hazardous Substances Data: 241479-74-3(Hazardous Substances Data)

Usage

Uses

(αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-methyl-1H-1,2,4-triazole-1-butanenitrile is an intermediate in the synthesis of Isavuconazole (I777830), an triazole based antifungal agent for the treatment of invasive fungal infections.

Upstream product

• 241479-73-2 (2R,3S)-2-(2,5-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)-methyl]-oxirane 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 241479-75-4 (2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanamide 
• 483340-19-8 (2R,3R)-3-[3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-3-(1H-1,2,4-triazol-1-yl)]butanoic acid 
• 483340-19-8 3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanoic acid 
• 241479-72-1 (2R,3R)-2-(2,5-difluoro-phenyl)-1-(1H-1,2,4-triazole-1-yl)butan-2,3-diol 
• 7677-24-9 trimethylsilyl cyanide 
• 367-30-6 2,5-difluoroaniline 
• 1157938-97-0 1-(2,5-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone 
• 2991-28-8 2,5-difluorobenzoic acid 
• 61380-66-3 [(1R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl]methanesulfonic acid 
• 107-12-0 propiononitrile 

Downstream Products

• 241479-67-4 Isavuconazole 
• 1286730-01-5 (2R,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)thiobutyramide hydrogensulphate 

Relevant articles and documents

AN IMPROVED PROCESS FOR THE PREPARATION OF TRIAZOLE DERIVATIVES

The present invention relates to an improved process for the preparation of triazole derivatives such as ravuconazole and isavuconazole.

Preparation method of isavuconazole intermediate

The invention provides a preparation method of an isavuconazole intermediate. Specifically, the present invention provides a method for preparing (2R,3S)-1-(1H-1,2,4-triazol-1-yl)-2-(2,5-difluorophenyl)-3-cyano-2-butanol (an intermediate 10) by carrying out a ring-opening reaction on (2R,3S)-2-(2,5-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]ethylene oxide (an intermediate 9) and trimethylcyanosilane in the presence of tetrabutylammonium fluoride (TBAF). The product obtained by the method provided by the invention has high purity and yield, and the method has mild conditions, iseasy to control, and is suitable for industrial mass production.

Preparation method of isavuconazole and isavuconazole prepared through method

The invention relates to a preparation method of isavuconazole and isavuconazole prepared through the method.The preparation method comprises the following steps that 1, diflurophenyl acetylchloride, triazole, CuI, potassium carbonate and first organic solvent are sequentially added into a reaction kettle, reacting under stirring is performed at the temperature of 80 DEG C-100 DEG C, and then purifying is performed to obtain a first product; 2, propionitrile, a catalyst and second organic solvent are added into a reaction container, the temperature is lowered to minus 20 DEG C-minus 5 DEG C, the second organic solvent containing the first product is dropwise added, reacting and purifying are performed to obtain a second product, and a mixture composed of C-9 primary amine quinine and copper pigment alkali is adopted as the catalyst; 3, the second product is added into another reaction container, diethylphosphorodithioate, water and mixed isopropanol solvent are added into the reaction container, heating is performed until the temperature is increased to 80 DEG C-90 DEG C, reacting under stirring and purifying are sequentially performed, and a third product is obtained; 4, the third product, 2-bromo-4'-acetylbenzonitrile and third organic solvent are mixed, react under stirring at the temperature of 60 DEG C-70 DEG C and then purified, and the isavuconazole is obtained.Accordingly, a novel synthetic route is redesigned, and the reaction steps are reduced.