Hydrochloric Acid → HCID 178440302, compound

Participants

Reaction Steps

A 100 mL round-bottomed flask equipped with rubber septum and nitrogen inlet needle was charged with 2-(4-(5-(2,4-difluorophenyl)-4-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-oxoethyl acetate (0.145 g, 0.277 mmol, prepared using General Procedure T from 6-(3-(2,4-difluorophenyl)-2-(piperidin-4-yl)-1H-imidazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (Example #Q.1.2) and acetoxyacetyl chloride) in THF (5.0 mL). A 2.5M aqueous NaOH solution (0.274 mL, 0.685 mmol) was added dropwise via syringe to give a yellow solution. The reaction mixture was stirred at about ambient temperature for about 20 min. Additional 2.5M aqueous NaOH (0.274 mL, 0.685 mmol) was added dropwise via syringe. The reaction mixture was stirred at about ambient temperature for about 1 h. The solution was acidified with 1N HCl to about pH 5. The reaction mixture was partitioned between DCM and water. The layers were separated and the organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography using DCM/MeOH (gradient, 1:0 to 9:1) to provide the title compound (0.107 g, 80%): LC/MS (Table 1, Method b) Rt=1.7 min; MS m/z: 482.2 (M+H)+.

Provenance & Evidence