Water → 7-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Participants

Reaction Conditions

Reaction Steps

To N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxamide (1.382 mmol, 500 mg) in ethyl acetate (5 ml) at 0° C. was added phosphorus oxychloride (5.53 mmol, 0.515 ml). The reaction mixture was stirred at room temperature for two days and at 60° C. for one day. The reaction mixture was cooled to 0° C., an excess solid sodium hydrogencarbonate was added and the suspension was stirred at 0° C. for 10 minutes and at room temperature for 20 minutes. Then the suspension was again cooled to 0° C., water was added and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane applying a gradient 0 to 10% methanol) to give 7-(8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (119 mg).

Provenance & Evidence