Diisopropylethylamine → (S)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 2.37 g, 6.0 mmol) and (S)-pyrrolidin-3-ol (0.627 g, 7.2 mmol) were dissolved in iPrOH (6 mL). DIPEA (2.1 mL, 12 mmol) was added and the RM mixture was heated at 140° C. for 1 h in a MW vial. After cooling to RT, the RM was dissolved in EtOAc, and washed with 0.5 M HCl and brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure until the crystallization began. The mixture was triturated with n-pentane, filtered and dried to afford the title compound as a beige crystalline solid. HPLC (Condition 4) tR=5.51 min, UPLC-MS (Condition 3) tR=1.09 min, m/z=448.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.74-2.03 (m, 2H) 3.55 (d, J=11.34 Hz, 1H) 3.64-3.74 (m, 1H) 3.78-3.89 (m, 2H) 4.33 (br. s, br. s, 1H) 4.97 (d, J=3.13 Hz, 1H) 7.33 (d, J=8.99 Hz, 2H) 7.78-7.90 (m, 2H) 8.32 (d, J=1.56 Hz, 1H) 8.63-8.72 (m, 1H) 10.20 (s, 1H).

Provenance & Evidence