反应详情

A mixture of (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.2, 60 mg, 0.134 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (42 mg, 0.202 mmol), Pd(PPh3)2Cl2 (9.44 mg, 0.013 mmol), Na2CO3 (42.8 mg, 0.403 mmol), DME (570 μL), water (163 μL) and EtOH (81 μL) in a MW vial was sealed, evacuated/purge with argon and subjected to MW irradiation at 120° C. for 10 min. The RM was diluted with THF (1 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 46.7 mg, 0.067 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 9, 25% for 0.2 min then 15% to 45% in 14 min) to yield the title compound as a white solid. LC-MS (Condition 2) tR=1.61 min, m/z=448.2/449.2 [M+H]+, m/z=446.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.71-1.80 (m, 1H) 1.81-1.91 (m, 1H) 2.98 (d, J=11.25 Hz, 1H) 3.25-3.39 (m, 0.2H) 3.44-3.53 (m, 1H) 3.89 (s, 3H) 4.22 (s, 1H) 4.84 (s, 1H) 7.34 (d, J=8.56 Hz, 2H) 7.53 (s, 1H) 7.84 (d, J=5.38 Hz, 2H) 7.86-7.88 (m, 1H) 7.94 (d, J=2.45 Hz, 1H) 8.67 (d, J=2.45 Hz, 1H) 10.14 (s, 1H).

1. customwas sealed
2. customevacuated/purge with argon
3. customsubjected to MW irradiation at 120° C. for 10 min
4. additionThe RM was diluted 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 preparative HPLC (Condition 9, 25% for 0.2 min