6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide → 6-(cis-3-(Aminomethyl)-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

Participants

Reaction Steps

The title compound was prepared in an analogous fashion to that described in Example 48 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1) and cis-4-(aminomethyl)pyrrolidin-3-ol dihydrochloride (Stage 80.1). The crude product was purified by preparative HPLC (Condition 10). Fractions containing product were combined, treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure to give an aq. residue which was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue was suspended in DCM/n-hexane, filtered and dried to afford the title product as a beige solid. HPLC (Condition 7) tR=5.38 min, UPLC-MS (Condition 3) tR=0.78 min, m/z=479 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.85-2.05 (m, 1H) 2.38-2.86 (m, 2H) 2.88-3.06 (m, 1H) 3.08-3.23 (m, 1H) 3.24-3.37 (m, 2H) 3.91-4.18 (m, 1H) 6.33-6.42 (m, 1H) 7.32 (d, J=8.60 Hz, 2H) 7.68-7.91 (m, J=9.00 Hz, 3H) 7.97-8.06 (m, 1H) 8.68-8.78 (m, 1H) 10.20 (s, 1H) 12.94 (br. s, 1H).

Provenance & Evidence