3,3-Difluoropyrrolidine hydrochloride → N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3,3-difluoropyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

Participants

Reaction Steps

The title compound was prepared in an analogous fashion to that described in Example 224 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide (Stage 247.1) and 3,3-difluoropyrrolidine hydrochloride (no extraction with citric acid). After purification by flash chromatography on Silica gel, the residue was suspended in iPr2O (10 mL) and stirred for 30 min. Crystals were filtrated off, washed with iPr2O (10 mL) and dried to afford the title product as a white solid. HPLC (Condition 10) tR=7.198 min, UPLC-MS (Condition 3) tR=1.12 min, m/z=482 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.39 (spt, J=7.14 Hz, 2H) 3.37 (t, J=7.23 Hz, 2H) 3.62 (t, J=12.90 Hz, 2H) 7.36 (d, J=8.21 Hz, 2H) 7.87 (d, J=8.99 Hz, 2H) 8.15 (s, 1H) 8.82 (s, 1H) 8.94 (s, 2H) 9.23 (s, 1H) 10.28 (s, 1H).

Provenance & Evidence