Formaldehyde → HCID 10408841, compound

Participants

Reaction Conditions

Reaction Steps

4-(3-chloro-2-fluoroanilino)-6-[(3R)-pyrrolidin-3-yloxy]-7-methoxyquinazoline hydrochloride (0.24 g, 0.56 mmole; prepared as described in Example 29-preparation of starting materials) was dissolved in formic acid (4 ml) and formaldehyde (37% w/v in water) (2 ml) was added. The mixture was heated to 85° C. for one hour and then evaporated under vacuum and azeotroped with toluene. The residue was partitioned between ethyl acetate and saturated aqueous NaFfCO3. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (94/6). The fractions containing the expected product were combined, evaporated and the residue triturated with isohexane/diethylether, filtered and dried under vacuum to give the title product as a white solid (0.13 g; 59%); 1H NMR Spectrum: (DMSO d6) 1.70-1.9 (m, 1H); 2.27 (s, 3H); 2.30-2.50 (m, 2H); 2.55-2.75 (na, 2H); 2.91-3.00 (m, 1H); 3.91 (s, 3H); 4.90-5.10 (m, 1H); 7.18 (s, 1H); 7.20-7.35 (m, 1H); 7.40-7.58 (m, 2H); 7.64 (s, 1H); 8.35 (s, 1H); 9.57 (s, 1H); Mass Spectrum: (M−H)− 401.

Provenance & Evidence