Piperazin-2-one → (rac)-4-{3-[1-(6-Fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-piperazin-2-one

Participants

Reaction Conditions

Reaction Steps

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Intermediate G, 100 mg, 0.303 mmol), KF (88 mg, 1.5 mmol), piperazin-2-one (91 mg, 0.91 mmol) were suspended in NMP (1 mL). The RM was stirred at 180° C. for 2 h. The mixture was diluted with EtOAc and washed with 1M Na2CO3 (1×) and water (2×). The aqueous was further extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by preparative UPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and were lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3 to remove the TFA salt. The filtrate was evaporated and the residue was triturated with pentane. The precipitate was filtered off and dried to afford the title compound as a white solid (tR 0.88 min (conditions 4), MH+=394, 1H-NMR in DMSO-d6: 8.10 (br. s, 1H); 7.95-7.87 (m, 2H); 7.65 (s, 1H); 7.51 (s, 1H); 7.54 (d, 1H); 7.49 (s, 1H); 7.22 (d, 1H); 4.79 (q, 1H); 3.95 (s, 4H); 3.87-3.78 (m, 1H); 3.67-3.55 (m, 2H); 3.22 (dd, 1H); 3.29-3.14 (m, 1H); 1.71 (d, 3H)).

Provenance & Evidence