1,2-Dimethoxyethane → 6-((2-Hydroxyethyl)(methyl)amino)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Steps

5-Bromo-6-((2-hydroxyethyl)(methyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 151.1, 59 mg, 0.136 mmol), pyrimidin-5-ylboronic acid (33.7 mg, 0.272 mmol), Pd(PPh3)2Cl2 (9.54 mg, 0.014 mmol) and Na2CO3 (57.6 mg, 0.544 mmol) were added to a MW vial and treated with a mixture of DME (576 μL), water (165 μL) and EtOH (82 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min, diluted with DME (3 mL) and treated with Si-Thiol (Silicycle, 1.44 mmol/g, 56.6 mg, 0.082 mmol). The RM was 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 DEAP, from 10% to 15% in 10 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=0.92 min, m/z=434.3 [M+H]+, m/z=432.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.71 (s, 3H) 3.44-3.52 (m, 2H) 3.53-3.60 (m, 2H) 4.68 (t, J=5.14 Hz, 1H) 7.36 (d, J=8.41 Hz, 2H) 7.82-7.90 (m, 2H) 8.15 (d, J=2.38 Hz, 1H) 8.77 (d, J=2.38 Hz, 1H) 8.97 (s, 2H) 9.19 (s, 1H) 10.23 (s, 1H).

Provenance & Evidence