Formaldehyde → HCID 10454614, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2R)-pyrrolidin-2-ylmethoxy]quinazoline hydrochloride (250 mg) (Prepared as described in Example 32), formic acid (5 ml) and formaldehyde (37% w/v in water) (2.5 ml) was heated to 85° C. for one hour. The reaction mixture was then evaporated under vacuum, azeotroped with toluene and partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated. The residues were then purified by flash chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (98/2-94/6). The fractions containing the desired product were combined and evaporated to give a colourless gum, which was triturated with diethylether, filtered and dried under vacuum to give the title product as a white solid (0.15 g); 1H NMR Spectrum: (DMSO d6) 1.55-1.83 (m, 3H); 1.95-2.10 (m, 1H); 2.20-2.35 (m, 1H); 2.45 (s, 3H); 2.68-2.85 (m, 1H); 2.93-3.10 (m, 1H); 3.92 (s, 3H); 1924.15 (m, 2H); 7.19 (s, 1H); 7.20-7.30 (m, 1H); 7.40-7.55 (m, 2H); 7.81 (s, 1H); 8.36 (s, 1H); 9.57 (s, 1H); Mass Spectrum: (M+H)+ 417.

Provenance & Evidence