Cyclopropanecarboxaldehyde → 3-Cyclopropyl-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

The 2-(2,4-difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (5.00 g, 15.2 mmol, Example #35, Step E) was reacted with cyclopropanecarbaldehyde (1.60 g, 22.8 mmol) overnight at ambient temperature in DCM (300 mL). The reaction mixture was cooled to about 0-4° C. Iodobenzene diacetate (5.4 g, 16.75 mmol) was added and the reaction mixture stirred at about 0-4° C. for about 30 min and then at ambient temperature for about 3 h. The reaction mixture was partitioned between DCM and a saturated aqueous Na2CO3 solution. The aqueous phase was back-extracted with of DCM (2×50 mL). The combined organics were dried over MgSO4, filtered, concentrated and purified by chromatography on silica gel using DCM/MeOH (gradient, 100:0 to 95:5) and subsequently triturated with a 90:10 mixture of DCM/Et2O to give the title compound (3.7 g, 64%): LC/MS (Table 1, Method a) Rt=2.22 min; MS m/z: 379.3 (M+H)+; 1H NMR (CDCl3) δ 7.84 (d, 1H), 7.66 (m, 1H), 7.08-7.00 (m, 1H), 6.95-6.85 (m, 2H), 4.55-4.45 (m, 2H), 3.12-3.01 (m, 2H), 2.78 (m, 2H), 2.53-2.42 (m, 1H), 1.45-1.38 (m, 2H), 1.28-1.19 (m, 2H).

Provenance & Evidence