Formaldehyde → HCID 10070557, compound

Participants

Reaction Conditions

Reaction Steps

6-{[(1-tert-Butoxycarbonyl)piperidin-4-yl]oxy}-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline (Reference Example 3; 300 mg, 0.66 mmol) was dissolved in formic acid (10 ml). Aqueous formaldehyde solution (40%, 1 ml) was added, and the mixture heated to 90° C. for 3 hours. The mixture was evaporated, and the residue dissolved in water (30 ml). The solution was adjusted to pH 8-9 by the addition of sodium hydroxide solution (1M), causing precipitation of a white solid; this was collected by filtration and washed with water (20 ml). The crude product was purified by chromatography, eluting with 0 to 2.5% (7:1 MeOH/concentrated aqueous NH4OH) in DCM. Evaporation of the appropriate fractions followed by crystallisation of the residue from acetonitrile gave the product as a white crystalline solid (55 mg, 20%); 1H NMR: 1.66-1.76 (m, 2H), 1.95-2.05 (m, 2H), 2.14-2.22 (m, 2H), 2.18 (s, 3H), 2.65-2.70 (m, 2H), 3.92 (s, 3H), 4.51 (m, 1H), 7.19 (s, 1H), 7.26 (dd, 1H), 7.47 (dd, 1H), 7.51 (dd, 1H), 7.78 (s, 1H), 8.34 (s, 1H), 9.53 (s, 1H); Mass Spectrum: 417.2, 419.3

Provenance & Evidence