Phosphorus oxychloride → HCID 25026888, compound

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)-2-(dimethylamino)acetohydrazide (25 mg, 0.0446 mmol) and toluene (3 ml). The reaction was stirred at 120° C. for 15 min. Then POCl3 (0.3 ml) was added and the reaction was stirred at 120° C. for additional 40 min. After this time, the solution was cooled to rt and the reaction mixture was concentrated. The residue was partitioned between EtOAc (30 ml) and NaHCO3 (sat, 20 ml). The organic layer was separated and washed with water (10 ml) and saturated NaCl (10 ml). The organic layer was then dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (4 g silica gel) eluting with a gradient of 0-80% EtOAc/CH2Cl2 to give product 4-(8-(4-chlorophenyl)-3-((dimethylamino)methyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)benzonitrile as an off white solid (10 mg, 39% yield).

Provenance & Evidence