Formic Acid → 3-(2-Chloro-phenyl)-6-fluoro-2-[(6-methyl-pyridin-2-ylamino)-methyl]-3h-quinazolin-4-one

Participants

Reaction Steps

A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.170 g, 0.56 mmol) and 2-amino-6-picoline (0.050 g, 0.46 mmol), in methanol (10 mL) was refluxed overnight. The reaction was concentrated and the residue was flash chromatographed on silica gel (25 g). Elution proceeded as follows: 10% ethyl acetate/hexane (500 mL), nil; 20% ethyl acetate/hexane (300 mL), nil; (100 mL), 0.082 g of intermediate imine; (300 mL), 0.192 g of a mixture of starting material and imine. The pure imine (0.082 g 0.21 mmol) was dissolved in ethanol (10 mL) and 10% palladium on carbon (0.082 g) and formic acid (0.357 mL, 9.45 mmol) were added. The reaction was stirred at ambient temperature for 24 hours. The reaction was carefully neutralized with sodium bicarbonate and then filtered through celite. The pad was well washed with ethyl acetate. The filtrate was concentrated to afford 0.068 g (82%) of 3-(2-chloro-phenyl)-6-fluoro-2-[(6-methyl-pyridin-2-ylamino)-methyl]-3H-quinazolin-4-one as a colorless oil which had: 1H NMR δ 7.92 (dd, J=3, 8 Hz, 1 H), 7.80 (dd, J=5, 9 Hz, 1 H), 7.65-7.64 (m, 1 H), 7.53-7.48 (m, 4 H), 7.43-7.40 (m, 1 H), 7.37-7.31 (m, 1 H), 6.47 (d, J=7 Hz, 1 H), 6.25 (d, J=8 Hz, 1 H), 4.18 (dd, J=5, 18 Hz, 1 H), 4.00 (dd, J=5, 18 Hz, 1 H), 2.37 (s, 3 H); APCI MS m/z=395 (P+1).

Provenance & Evidence