反应详情

A slurry of crude 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine (3-2, 88 mg, 0.179 mmol, 1.0 eq), 2-bromo-5-methylpyridine (92 mg, 0.537 mmol, 3.0 eq.), cesium carbonate (233 mg, 0.716 mmol, 4.0 eq.), palladium(II) acetate (4.02 mg, 0.018 mmol, 0.10 eq.), and butyldi-1-adamantylphosphine (19.26 mg, 0.054 mmol, 0.30 eq.) in toluene (1 ml) and water (300 μL) was heated at 100° C. for 16 hours. The solvent was removed by roto-evaporation and the resulting oil was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present) to afford 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(5-methylpyridin-2-yl)cyclopropyl)pyrimidine (3-3) as slightly yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.30 (d, 1H, J=2.0 Hz), 7.53 (s, 1H), 7.36 (dd, 1H, J=7.8, 2.2 Hz), 6.89 (d, 1H, J=2.0 Hz), 6.85 (dd, 1H, J=8.1, 2.2 Hz), 6.76 (d, 1H, J=8.1 Hz), 4.71 (s, 2H), 3.83 (s, 3H), 3.82 (s, 3H), 2.67 (bs, 4H), 2.62 (m, 1H), 2.42 (s, 3H), 2.29 (s, 3H), 1.84 (m, 2H). HRMS m/z (M+H) 495.1925 found, 495.1905 required.

1. customThe solvent was removed by roto-evaporation
2. customthe resulting oil was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present)