Phosphorus oxychloride → 4-Chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline

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Reaction Conditions

Reaction Steps

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol from Example 2 Step D (1.82 g, 6.25 mmol) was added phosphorousoxychloride (20 mL) and the mixture was heated at 95° C. for 3 h. The mixture was concentrated under reduced pressure and then toluene (20 mL) was added and evaporated. The residue was dissolved in EtOAc and washed with saturated NaHCO3 (1×) and brine (1×), dried over Na2SO4, and concentrated. The residue was purified by silica gel chromatography eluting with 10-80% EtOAc/hexanes to afford 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline (1.59 g, 82%). 1H NMR (300 MHz, DMSO-d6) δ 8.61 (d, J=2.6 Hz, 1H), 8.38 (d, J=8.3 Hz, 1H), 8.17-8.29 (m, 2H), 8.06-8.15 (m, 1H), 7.96-8.06 (m, 2H); LC-MS (ESI) m/z 310 (M+H)+.

Provenance & Evidence