Acetone → Benzonitrile, 4-[8-(4-chlorophenyl)-5,6-dihydro-3-(hydroxyMethyl)-5-[[2-Methyl-6-(trifluoroMethyl)-3-pyridinyl]Methyl]-6-oxo-1,2,4-triazolo[4,3-b]pyridazin-7-yl]-

Participants

Reaction Steps

To a round bottom flask was added 4-(3-(chloromethyl)-8-(4-chlorophenyl)-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 (30 mg, 0.053 mmol), sodium iodide (40 mg, 0.264 mmol) and acetone (2 ml). The reaction was stirred at room temperature for 8 hr. After this time, water (0.3 ml) was added followed by 1 drop of 1N NaOH. The reaction was stirred at room temperature for an additional 14 hrs. The solution was then diluted with EtOAc (25 ml) and washed with water (2×15 ml) and saturated NaCl (15 ml). The organic layer was dried (MgSO4), filtered and concentrated. The crude material was purified using an ISCO automated chromatography system (4 g silica gel, 20%-50% EtOAC/CH2Cl2) to give the product 4-(8-(4-chlorophenyl)-3-(hydroxymethyl)-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 a white solid (15 mg, 51% yield). HPLC retention time 2.990 min (Method A); LCMS (M+1)=551.0. 1HNMR (CDCl3, 500 Hz) 7.61(2H, d, J=8.25 Hz), 7.52(1H, d, J=7.7 Hz), 7.30-7.37(7H, m), 6.05(2H, s), 4.60(2H, s), 2.78(3H, s); 13CNMR (CDCl3, 500 Hz) 161.00, 158.90, 156.25, 146.20, 144.10, 137.10, 136.80, 132.80, 131.96, 131.74, 129.90, 129.09, 118.00, (m), 113.00, 100.00, 55.10, 49.10, 22.10.

Provenance & Evidence