1,2-Dimethoxyethane → 6'-(Hydroxymethyl)-2-morpholino-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Participants

Reaction Steps

5-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 148.1, 60 mg, 0.134 mmol), (6-(hydroxymethyl)pyridin-3-yl)boronic acid (41.1 mg, 0.269 mmol), Pd(PPh3)2Cl2 (9.44 mg, 0.013 mmol) and Na2CO3 (42.8 mg, 0.403 mmol) were added to a MW vial and treated with a mixture of DME (570 μL), water (163 μL) and EtOH (81 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min and then at 130° C. for 20 min, diluted with DME (2 mL) and treated with Si-Thiol (Silicycle, 1.44 mmol/g, 46.7 mg, 0.067 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 2-EP, from 15% to 20% in 6 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=0.95 min, m/z=475.4 [M+H]+, m/z=473.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.07-3.22 (m, 4H) 3.48-3.62 (m, 4H) 4.63 (s, 2H) 5.54 (br. s, 1H) 7.38 (d, J=8.53 Hz, 2H) 7.60 (d, J=8.03 Hz, 1H) 7.82-7.92 (m, 2H) 8.11 (d, J=8.28 Hz, 1H) 8.13-8.16 (m, 1H) 8.75-8.79 (m, 1H) 8.79-8.86 (m, 1H) 10.38 (br. s, 1H).

Provenance & Evidence