Sodium Carbonate → HCID 89907351, compound

Participants

Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 60 mg, 0.152 mmol), (Rac.)-pyrrolidin-3-ol (15.86 mg, 0.182 mmol), and DIPEA (53.0 μL, 0.303 mmol) in iPrOH (250 μL) were added to a MW vial and subjected to MW irradiation at 110° C. for 20 min. The RM was then transferred into a MV vial containing pyrimidin-5-ylboronic acid (56.4 mg, 0.455 mmol), Pd(PPh3)2Cl2 (10.65 mg, 0.015 mmol), Na2CO3 (80 mg, 0.758 mmol) and treated with a mixture of DME (600 μL)-water (200 μL). The vial was sealed, evacuated/purged with argon and the RM was subjected to MW irradiation at 80° C. for 2 h. The RM was cooled to RT, diluted with THF (1.5 mL), treated with Si-Thiol (Silicycle, 59.7 mg, 0.076 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 13, 30% for 0.2 min then 30% to 60% in 12 min) to yield the title compound as a white solid. UPLC-MS (condition 1) tR=2.01 min, m/z=446.0 [M+H]+, m/z=444.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.79 (m, 1H) 1.79-1.90 (m, 1H) 2.88 (d, J=11.0 Hz, 1H) 3.18-3.27 (m, 2H) 3.38-3.43 (m, 1H) 4.17-4.25 (m, 1H) 4.79-5.01 (m, 1H) 7.35 (d, J=8.3 Hz, 2H) 7.85 (d, J=4.9 Hz, 2H) 8.10 (d, J=2.4 Hz, 1H) 8.79 (d, J=2.4 Hz, 1H) 8.89 (s, 2H) 9.19 (s, 1H) 10.18 (s, 1H).

Provenance & Evidence