(αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile Chemical Properties

Melting point:

112-115oC

Boiling point:

522.5±60.0 °C(Predicted)

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)

form 

Solid

color 

Pale Yellow

InChI

InChI=1/C13H12F2N4O/c1-9(5-16)13(20,6-19-8-17-7-18-19)11-4-10(14)2-3-12(11)15/h2-4,7-9,20H,6H2,1H3/t9-,13+/s3

InChIKey

SYSUFNUKZJVPBI-OWKUYNCVNA-N

SMILES

N1(C[C@@](C2=CC(F)=CC=C2F)(O)[C@@H](C)C#N)C=NC=N1 |&1:2,12,r|

(αS,βR)-β-(2,5-Difluorophenyl)-β-hydroxy-α-Methyl-1H-1,2,4-triazole-1-butanenitrile Usage And Synthesis

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.

Synthesis

(B) In a three-necked reaction flask equipped with a stirrer, propionitrile (4 mol), catalyst (0.1 mol containing 0.05 mol of C-9 cinchona alkaloid-derived primary amine and 0.05 mol of copper complex), benzoic acid (0.1 mol), and N,N-dimethylacetamide (DMA, 0.5 L) were added sequentially. The reaction mixture was cooled to -10 °C with continuous stirring. Subsequently, N,N-dimethylacetamide solution (0.3 L) containing 1-(2,5-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (1 mol) was slowly added dropwise, keeping the reaction temperature at -10 °C. The progress of the reaction was monitored by thin layer chromatography (TLC) until the reaction was complete. Upon completion of the reaction, the reaction was quenched by the addition of hydrochloric acid solution (1 mol / 0.3 L) and then extracted with ethyl acetate (0.2 L x 3). The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give an oil. The oily substance was treated with a solvent mixture of n-heptane/dichloromethane (1:1, v/v), and after recrystallization, filtration and drying, (2S,3R)-3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile was obtained in off-white solid form in a yield of 80%, with an diastereoisomer ratio (dr) of 97:3.

References

[1] Patent: CN105777740, 2016, A. Location in patent: Paragraph 0019; 0024