反应详情

2′-Methyl-5′-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1′-biphenyl-4-carboxylic acid (40 mg, 0.1 mmol), HATU (38 mg, 0.1 mmol), HOBT (13 mg, 0.1 mmol), DIPEA (52 μl), and 1-methylpiperazine (15 mg, 0.12 mmol) were mixed in DMF (1 ml) and stirred at room temperature for 18 h. The solvent was evaporated under vacuum and the residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml). The organic phase was applied to a silica gel flash column and eluted with DCM/ethanol/ammonia (100:8:1 then 40:8:1), which after evaporation of the solvents under vacuum gave N-{6-methyl-4′-[(4-methylpiperazin-1-yl)carbonyl]-1,1′-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide (14 mg, 29%). NMR; δH [2H6]-DMSO 10.26,(1H, s), 8.19,(1H, d), 7.69–7.67,(2H, m), 7.47–7.41,(4H, m), 7.29,(1H, d), 6.96,(1H, d), 6.86,(1H, s), 3.59,(2H, b), 3.43,(4H, m), 2.33,(6H, b), 2.21,(3H, s), 2.21,(3H, s), 1.95,(4H, m). MS: MH+484.

1. customThe solvent was evaporated under vacuum
2. customthe residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml)
3. washeluted with DCM/ethanol/ammonia (100:8:1
4. custom40:8:1), which after evaporation of the solvents under vacuum