Hydrochloric Acid → 6-(3,5-difluorophenyl)-2-[(3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazol-5-yl)methyl]pyridazin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

4-[4-(5-{[3-(3,5-difluorophenyl)-6-oxopyridazin-1(6H)-yl]methyl}-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoic acid (218 mg; 0.22 mmol; 1.0 eq.) was added in one portion to a suspension of 1,1′-carbonyldiimidazole (97 mg; 0.60 mmol; 2.7 eq.) in DMF (20 mL). The reaction suspension was heated at 10° C. for 20 min then morpholine (100 μl; 1.15 mmol; 5.2 eq.) was added in one portion. The reaction mixture was heated at 100° C. for 16 h. It was allowed to cool to RT, poured into HCl (1N solution) and extracted with EtOAc. Combined organic phases were washed sequentially with an aqueous saturated solution of NaHCO3 and brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by preparative HPLC to give the title compound a a white solid. 1H NMR (300 MHz, DMSO-d6) δ 13.42 (s, 1H), 9.38 (s, 1H), 8.48 (s, 1H), 8.23-8.08 (m, 3H), 7.75-7.64 (m, 4H), 7.61 (d, J=8.6 Hz, 1H), 7.57-7.48 (m, 1H), 7.42-7.28 (m, 1H), 7.13 (d, J=9.8 Hz, 1H), 5.51 (s, 2H), 3.64 (s, 8H). HPLC (Condition A): Rt 3.78 min (purity 97.7%). MS (ESI−): 593.7.

Provenance & Evidence