反应详情

Stir together 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (1.6 g, 8.43 mmol) and 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (2.35 g, 12.6 mmol) in dry tetrahydrofuran (10 mL) at room temperature for 15 min., under nitrogen. Add sodium triacetoxyborohydride (2.68 g, 12.6 mmol) and stir reaction for 1 hr. Quench reaction mixture with saturated aq. sodium bicarbonate (50 mL), then extract with DCM (3×50 mL) and pass through an IST Phase Separator Frit®. Concentrate and purify (silica gel chromatography, eluting with 5:95 methanol:DCM) and concentrate all fractions containing product. Pass the mixture through a CBA column to retain the product, wash with methanol and then elute with 2 M ammonia in methanol. Recrystallize from hot ethanol and dry in vacuum oven to give 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as white crystals (2.08 g, 65%). MS (ES): m/z=369 [M+H]+.

1. customreaction for 1 hr
2. customQuench
3. customreaction mixture with saturated aq. sodium bicarbonate (50 mL)
4. extractionextract with DCM (3×50 mL)
5. concentrationConcentrate
6. custompurify
7. wash(silica gel chromatography, eluting with 5:95 methanol:DCM)
8. concentrationconcentrate all fractions
9. additioncontaining product
10. washwash with methanol
11. washelute with 2 M ammonia in methanol
12. customRecrystallize from hot ethanol
13. customdry in vacuum oven