反应详情

According to the method described in WO2007007886, sodium hydride (50% oily product) (314 mg) was added to methylthioethanol (7.88 mL) under cooling with ice and stirring, and then copper (490 mg) and 2-amino-5-bromopyrazine (1.00 g) were added thereto. The reaction mixture was placed in an autoclave and heated and stirred at 160° C. for about 5 hours. After cooling, the reaction mixture was diluted with water (50 mL) and ethyl acetate (50 mL), and 25% aqueous ammonia (2 mL) was added to the mixture to make it basic. The reaction mixture was filtrated through Celite, and the organic layer and the aqueous layer were separated. The aqueous layer was extracted with ethyl acetate (50 mL×2), and the extracts and the organic layer were combined, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1) and then by preparative TLC (chloroform:methanol=10:1, then NH silica gel, hexane:acetone=3:1) to give the title compound as white powder crystals (59.2 mg, yield: 6%).

1. temperatureunder cooling with ice
2. temperatureheated
3. stirringstirred at 160° C. for about 5 hours
4. temperatureAfter cooling
5. additionwas added to the mixture
6. filtrationThe reaction mixture was filtrated through Celite
7. customthe organic layer and the aqueous layer were separated
8. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltrated
11. customThe solvent was evaporated under reduced pressure
12. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1)