Azetidine-1-carbothiohydrazide → 6-(2-(2,4-Difluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.61 g, 1.54 mmol; Preparation #A.2) and azetidine-1-carbothiohydrazide (0.29 g, 2.20 mmol) in HOAc (5 mL) was stirred at about 55° C. for about 1-2 h. The reaction mixture was cooled to ambient temperature overnight and partitioned between DCM and water. The aqueous layer was basified with a saturated aqueous solution of Na2CO3 and extracted with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting crude material was purified by chromatography on silica gel using DCM/MeOH (gradient, 100:0 to 90:10), stirred overnight with Et2O/DCM (100:10), and collected by vacuum filtration to give the title compound (0.16 g, 26%): LC/MS (Table 1, Method a) Rt=2.98 min; MS m/z: 396.2 (M+H)+; 1H NMR (CDCl3) δ 7.76 (d, J=9.89 Hz, 1H), 7.56-7.51 (m, 1H), 7.11-6.99 (m, 1H), 6.98-6.87 (m, 1H), 6.73 (dd, J=9.89, 1.83 Hz, 1H), 6.44 (s, 1H, broad), 4.2 (t, J=6.08 Hz, 2H), 3.61-3.58 (m, 2H), 3.56-3.52 (m, 1H), 2.36-2.24 (m, 2H), 1.58 (d, J=6.99 Hz, 6H).

Provenance & Evidence