Tributylphosphine → HCID 22625100, compound

Participants

Reaction Conditions

Reaction Steps

1-(3-Hydroxypropyl)-1,4-dihydro-4-pyridone (220 mg, 1.44 mmol) in methylene chloride (4 ml) followed by 1,1′-(Azodicarbonyl)dipiperidine (720 mg, 2.86 mmol) were added to a stirred solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (300 mg, 0.94 mmol), (prepared as described for the starting material in Example 15), and tributylphosphine (0.69 ml, 2.8 mmol) in methylene chloride (20 ml) under nitrogen at 5° C. The mixture was stirred at 5° C. for 3 hours, allowed to warm to ambient temperature and stirred for a further 18 hours. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic phase was separated, dried (MgSO4), and solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/triethylamine mixtures (100/0/0 increasing to 70/30/0.5) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-[3-(4-oxo-1,4-dihydro-1-pyridyl)propoxy]quinazoline (48 mg, 11%). m.p. >250° C. 1H NMR Spectrum: (DMSOd6) 3.56(m, 2H); 4.00(s, 3H); 3.54(t, 2H); 4.38(t, 2H); 7.42(d, 1H); 7.5-7.65(m, 5H); 8.43(s, 1H); 8.65-8.75(m, 4H) MS-ESI: 455 [MH]+

Provenance & Evidence