反应详情

温度

85 °C

To a solution of (2S)-2-{[(S)-(4-bromophenyl)(thien-2-yl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide, from example 20, step 3 (113 mg, 0.27 mmol) in DMF (3 mL) was added 4-piperazin-1-ylphenylboronic acid (73 mg, 0.30 mmol), and a 2.0M aqueous solution of Na2CO3 (0.54 mL, 1.08 mmol). The mixture was placed under vacuum and purged with nitrogen 3 times before the PdCl2(dppf)2 was added (10 mg, 0.014 mmol). The reaction mixture was purged 3 other times with nitrogen and the reaction was heated to 85° C. for 16 hours. The mixture was then diluted with dichloromethane and filtered over celite. The organic layer was isolated and washed with a saturated solution of NaHCO3 and brine, dried and evaporated. The crude residue was chromatographed on silica gel using 1% NH4OH and 9% methanol in dichloromethane to afford the title compound.

1. custompurged with nitrogen 3 times before the PdCl2(dppf)2
2. additionwas added (10 mg, 0.014 mmol)
3. customThe reaction mixture was purged 3 other times with nitrogen
4. additionThe mixture was then diluted with dichloromethane
5. filtrationfiltered over celite
6. customThe organic layer was isolated
7. washwashed with a saturated solution of NaHCO3 and brine
8. customdried
9. customevaporated
10. customThe crude residue was chromatographed on silica gel using 1% NH4OH and 9% methanol in dichloromethane