反应详情

3-Bromo-4-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 11.1, 83 mg, 0.18 mmol), pyrimidin-5-ylboronic acid (66.9 mg, 0.540 mmol) and Na2CO3 (57.2 mg, 0.540 mmol) were added to a MW vial and treated with a mixture of DME (764 μL), water (218 μL) and EtOH (109 μL). The vial was sealed, evacuated/purged with argon and the RM was subjected to MW irradiation at 80° C. for 2 h. The RM was cooled to RT, diluted with THF (1 mL) and treated with Si-Thiol (Silicycle, 1.27 mmol/g, 70.9 mg, 0.090 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (8:2), from 20% to 70% EtOAc-EtOH+0.1% NH4OH (8:2)) to yield the title compound as a yellow solid. UPLC-MS (condition 1) tR=2.47 min, m/z=459.0 [M+H]+, m/z=457.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.19 (s, 3H) 1.68-1.83 (m, 2H) 2.77 (d, J=9.78 Hz, 1H) 2.87 (d, 1H) 2.97-3.07 (m, 1H) 3.21-3.30 (m, 1H) 4.72 (s, 1H) 6.96 (d, J=9.05 Hz, 1H) 7.33 (d, J=8.56 Hz, 2H) 7.80-7.89 (m, 3H) 7.94 (dd, J=8.93, 2.32 Hz, 1H) 8.86 (s, 2H) 9.16 (s, 1H) 10.09 (s, 1H), 9.29 ppm.

1. customThe vial was sealed
2. customevacuated/purged with argon
3. customthe RM was subjected to MW irradiation at 80° C. for 2 h
4. additiondiluted with THF (1 mL)
5. filtrationfiltered
6. customthe filtrate was evaporated off under reduced pressure
7. customto give a residue which
8. customwas purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (8:2), from 20% to 70% EtOAc-EtOH+0.1% NH4OH (8:2))