反应详情

温度

85 °C

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-isochroman-1-ylmethyl-amine (141 mg, 0.46 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl-boronic acid (125 mg, 0.6 mmol), and Cs2CO3 (0.37 g, 1.15 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL) is degassed by bubbling with Ar gas for 5 minutes, and treated with tetrakis(triphenylphosphine)palladium(0) (27 mg, 0.023 mmol) at room temperature. The mixture is heated at 85° C. for 3 h. The mixture is diluted with H2O (20 mL), and extracted with EtOAc (20 mL). The aqueous layer is separated, acidified to pH 2.5 with 1M HCl solution, and extracted with EtOAc (2×30 mL). The extracts are dried (MgSO4), filtered through a short pad of SiO2 to afford 2-(3-{6-[(isochroman-1-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (189 mg, Example 91). LCMS: RT=2.03 minutes; MS: 434 (M+H); 1H NMR (300 MHz, CDCl3) □9.8 (1H, s), 8.02 (1H, s), 7.82 (1H, d, J=6 Hz), 7.5-7.1 (6H, m), 6.43 (1H, s) 5(1H), 4 (3H, s), 3.85-3.75 (1H, m), 3.65-3.55 (1H, m), 3.04-2.95 (1H, m), 2.75 (1H), 1.8 (6H, s). IC50=23 nM

1. customis degassed
2. customby bubbling with Ar gas for 5 minutes
3. extractionextracted with EtOAc (20 mL)
4. customThe aqueous layer is separated
5. extractionextracted with EtOAc (2×30 mL)
6. dry with materialThe extracts are dried (MgSO4)
7. filtrationfiltered through a short pad of SiO2