1,2-Dimethoxyethane → 4-(cis-3,4-Dihydroxypyrrolidin-1-yl)-3-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Participants

Reaction Steps

3-Bromo-4-((3S,4R)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 10.1, 60 mg, 0.13 mmol), pyrimidin-5-ylboronic acid (32.2 mg, 0.260 mmol), Pd(PPh3)2Cl2 (9.11 mg, 0.013 mmol) and Na2CO3 (55.0 mg, 0.519 mmol) were added to a MW vial and treated with a mixture of DME (551 μL), water (157 μL) and EtOH (79 μL). Vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 10 min. The RM was diluted with DME (3 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 54.1 mg, 0.078 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 DEAP, isocratic 25% in 9 min.) to yield the title compound as a white solid. UPLC-MS (Condition 3) tR=0.83 min, m/z=462.1 [M+H]+, m/z=460.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.05 (dd, J=10.76, 4.16 Hz, 2H) 3.26 (dd, J=10.51, 4.89 Hz, 2H) 3.98 (t, J=3.91 Hz, 2H) 4.89 (br. s, 2H) 7.35 (d, J=8.56 Hz, 2H) 7.79-7.90 (m, 2H) 8.10 (d, J=2.20 Hz, 1H) 8.79 (d, J=2.20 Hz, 1H) 8.88 (s, 2H) 9.20 (s, 1H) 10.17 (s, 1H).

Provenance & Evidence