Sodium Carbonate → 2-(3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5'-fluoro-[3,3'-bipyridine]-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

2-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5′-fluoro-[3,3′-bipyridine]-5-carboxamide (Stage 266.1, 80 mg, 0.183 mmol) and DIPEA (0.224 mL, 1.282 mmol) were added to a vial containing iPrOH (2 mL) and 4-(aminomethyl)pyrrolidin-3-ol dihydrochloride (Stage 267.1, 37.1 mg, 0.192 mmol) was added under an argon atmosphere. The RM was stirred at 80° C. for 3 days. The RM was treated with sat. aq. Na2CO3 (20 mL) and extracted with EtOAc. The combined extracts were washed with brine (10 mL), dried over Na2SO4, filtered and evaporated to dryness under reduced pressure to give the crude product was purified by preparative HPLC (Condition 14). Fractions containing product were treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure. The resulting aq. residue was extracted with EtOAc and the combined extracts were dried over Na2SO4, filtered and evaporated. The residue was suspended in DCM/Et2O/n-hexane. The obtained solid was filtered off, washed with Et2O, n-hexane and dried to afford the title product as a white solid. HPLC (Condition 10) tR=5.74 min, UPLC-MS (Condition 3) tR=0.83 min, m/z=508 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.41-3.33 (m, 7H) 3.92-4.21 (m, 1H) 7.34 (d, J=8.99 Hz, 2H) 7.85 (d, J=9.38 Hz, 3H) 8.03-8.11 (m, 1H) 8.47-8.54 (m, 1H) 8.59 (m, J=2.70 Hz, 1H) 8.77 (m, J=2.30 Hz, 1H) 10.19 (s, 1H).

Provenance & Evidence