Ethylenediamine → (S)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

(S)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide (Stage 13.1), ethylenediamine (57.3 μL, 0.848 mmol) and 1 M TBAF in THF (848 μL, 0.848 mmol) was added to a MW vial, which was sealed and the RM was stirred at 80° C. for 24 h. The solvent was evaporated off under reduced pressure to give a residue which was dissolved in EtOAc (30 mL), washed 3 times with sat. aq. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product was purified by preparative SFC (Column 2-EP, from 20% to 25% in 6 min) to yield the title compound as a white solid. HPLC Chiral (CHIRALCEL® OD-H, 250×4.6 mm, eluent: n-heptane/EtOH/MeOH (80:12:8), 1 mL/min, UV 210 nm) tR=13.92 min, UPLC-MS (Condition 3) tR=0.93 min, m/z=448.2 [M+H]+, m/z=446.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.19 (s, 3H) 1.65-1.81 (m, 2H) 3.01 (d, J=11.54 Hz, 1H) 3.07 (d, J=10.92 Hz, 1H) 3.24-3.33 (m, 1H) 3.43-3.53 (m, 1H) 4.64-4.75 (m, 1H) 6.34-6.41 (m, 1H) 7.34 (d, J=8.66 Hz, 2H) 7.52-7.84 (m, 1H) 7.86 (d, J=9.16 Hz, 2H) 8.00-8.07 (m, 1H) 8.69-8.78 (m, 1H) 10.19 (s, 1H) 12.89-13.13 (m, 1H).

Provenance & Evidence