Formaldehyde → HCID 60036683, compound

Participants

Reaction Steps

A solution of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2S,4R)-1-(tert-butoxycarbonyl)-2-(morpholinocarbonyl)pyrrolidin-4-yloxy]quinazoline (0.3 g), formic acid (3.0 ml) and paraformaldehyde (0.047 mg) was stirred at 80° C. for 8 hours. The reaction was cooled, reduced under vacuum and adsorbed onto silica. The product was eluted with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the desired product were combined and evaporated under vacuum. The product was then re-purified by preparative HPLC on a reverse phase Hi-Chrom HIRPB column. The product was eluted with decreasingly polar mixtures of acetonitrile/water (0.1% trifluoroacetic acid) (20/80 to 50150). The fractions containing the desired product were combined and evaporated under vacuum and the residue dissolved in methylene chloride/methanol (saturated with ammonia) and adsorbed onto silica. The product was eluted with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 90/10). The fractions containing the desired product were combined and evaporated under vacuum to give the title product as a colourless foam (0.058 g); 1H NMR Spectrum: (DMSO d6) 2.10-2.18 (m, 1H), 2.31 (s, 3H), 2.53-2.60 (m, 1H), 3.44-3.67 (m, 10H), 3.72 (t, 1H), 3.92 (s, 3H), 5.10 (m, 1H), 7.21 (s, 1H), 7.28 (t, 1H), 7467.56 (m, 2H), 7.71 (s, 1H), 8.36 (s, 1H), 9.64 (s, 1H); Mass Spectrum: (M+H)+ 516.

Provenance & Evidence