Diisopropylethylamine → HCID 89907813, compound

Participants

Reaction Steps

A mixture of (R)-2-(3-hydroxypyrrolidin-1-yl)-5-((4-(trifluoromethoxy)phenyl)carbamoyl)nicotinic acid (Stage 72.3, 1.50 g, 3.65 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 1.66 g, 4.38 mmol) and DIPEA (0.566 g, 4.38 mmol) in DMF (40 mL) was stirred at RT for 15 min and then propargylamine (0.35 mL, 5.47 mmol) was added. The mixture was stirred for 3 h and then treated with EtOAc, washed with sat. aq. solution of NaHCO3 and brine. The organic phase was dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the residue was crystallized from TBME/EtOAc to afford the product as a colorless crystalline solid. m.p. 246-248° C., HPLC (Condition 4) tR=4.79 min, UPLC-MS (Condition 8) tR=0.89 min, m/z=449.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.78-2.01 (m, 2H), 3.15 (t, J=2.54 Hz, 1H), 3.24 (d, J=12.12 Hz, 1H), 3.43-3.69 (m, 3H), 4.03 (d, J=4.30 Hz, 2H), 4.33 (br. s, 1H), 4.96 (d, J=3.13 Hz, 1H), 7.34 (d, J=8.99 Hz, 2H), 7.79-7.90 (m, 2H), 8.04 (d, J=2.35 Hz, 1H), 8.75 (d, J=2.35 Hz, 1H), 8.96 (t, J=5.67 Hz, 1H), 10.20 (s, 1H).

Provenance & Evidence