1,2-Dimethoxyethane → (R)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Steps

(R)-5-Bromo-6-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 66.1, 60 mg, 0.130 mmol), pyrimidin-5-ylboronic acid (32.3 mg, 0.261 mmol), Pd(PPh3)2Cl2 (9.15 mg, 0.013 mmol) and Na2CO3 (41.5 mg, 0.391 mmol) were added to a MW vial and treated with a mixture of DME (553 μL), water (158 μL) and EtOH (79 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 120° C. for 10 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 45.3 mg, 0.065 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Silica, from 23% to 28% in 6 min) to yield the title compound as a white solid. UPLC-MS (Condition 3) tR=0.94 min, m/z=460.4 [M+H]+, m/z=458.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.20 (s, 3H) 1.67-1.83 (m, 2H) 2.96 (d, J=10.54 Hz, 1H) 3.03 (d, J=10.54 Hz, 1H) 3.18-3.26 (m, 1H) 3.38-3.47 (m, 1H) 4.75 (s, 1H) 7.36 (d, J=8.28 Hz, 2H) 7.82-7.90 (m, 2H) 8.10 (d, J=2.38 Hz, 1H) 8.79 (d, J=2.38 Hz, 1H) 8.89 (s, 2H) 9.20 (s, 1H) 10.19 (s, 1H).

Provenance & Evidence