Phosphorus oxychloride → HCID 20079569, compound

In 1,2-dichloroethane (5.0 ml) was dissolved N-(2-pyrazinylmethyl)chloroacetamide (0.50 g) followed by addition of phosphorus oxychloride (5.0 ml) at room temperature. The mixture was refluxed for 40 minutes and, then, concentrated under reduced pressure. The residue was dissolved in methanol (1.0 ml) followed by addition of diethyl ether to give crude 3-chloromethylimidazo[1,5-a]pyrazine hydrochloride as powder (0.46 g). This powder (0.18 g) was added to a mixture of (2RS,3RS)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol (0.25 g), ethanol (2.5 ml) and 28% sodium methoxide-methanol (0.36 ml) at room temperature and the mixture was stirred for 7 minutes. The reaction mixture was poured into water (20 ml) and extracted with ethyl acetate (20 ml×3). The organic layers were combined, washed with saturated aqueous sodium chloride solution (10 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (2 cm×8 cm), and elution was carried out with methanol-methylene chloride (5:95). The desired fractions were combined and further subjected to silica gel chromatography (2 cm×8 cm) and elution was carried out with methylene chloride-ethylacetate (1:2). The desired fractions were combined and concentrated. To the residue were added to a mixture of diethyl ether and hexane, whereupon (2RS,3RS)-2-(2,4-difluorophenyl)-3-(imidazo[1,5-a]pyradin-3-yl)methylthio-1-(1H-1,2,4-triazol-1-yl)-2-butanol (compound 5.7:0.02 g) was separated out as a colorless powder.

1. temperatureThe mixture was refluxed for 40 minutes
2. concentrationconcentrated under reduced pressure
3. dissolutionThe residue was dissolved in methanol (1.0 ml)
4. additionfollowed by addition of diethyl ether

ORD record

ord-dd508ce110664f498697840870bba5f2

Source dataset

uspto-grants-1995_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05405861