Potassium Carbonate → 2-(Tetrahydro-2H-pyran-2-yl)-5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3(2H)-one

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Reaction Steps

5-Hydroxy-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one (2.3 g, 12 mmol), 5-(bromomethyl)-2-(trifluoromethyl)pyridine (7.2 g, 30 mmol) and K2CO3 (8.4 g, 60 mmol) were stirred in DMF (40 ml) and CH2Cl2 (40 ml) for 48 h. The mixture was diluted with CH2Cl2, washed with 5% LiCl solution (4×) and concentrated. The residue was purified by column chromatography (40 g ISCO column column eluting with methylene chloride and a 10:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 95% methylene chloride) to yield the title compound (5.25 g, >100%) as a waxy white solid containing some DMF: 1H NMR (300 MHz, CDCl3) δ 8.78 (d, J=1.8 Hz, 1H), 7.97-7.88 (m, 1H), 7.76 (d, J=7.9 Hz, 1H), 7.72 (m, 1H), 6.20 (d, J=2.9 Hz, 1H), 6.03-5.98 (d, J=10.9, 2.0 Hz, 1H), 5.11 (s, 2H), 4.16-4.08 (m, 1H), 3.79-3.69 (m, 1H), 2.24-1.96 (m, 2H), 1.83-1.48 (m, 4H).

Provenance & Evidence