Benzaldehyde → 5-[(1R)-2-amino-1-methylethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine

Participants

Reaction Steps

Benzaldehyde (1.46 ml, 14.3 mmol) was added to a solution of 4-({5-[(1R)-2-amino-1-methylethoxy]quinazolin-4-yl}amino)-2-chlorophenol (obtained as described in Example 4.4, preparation of starting materials, 4.5 g, 13.08 mmol) in DMF (50 ml) and the mixture was stirred for 20 minutes. Potassium carbonate (7.23 g, 52.32 mmol), picolyl chloride hydrochloride (2.57 g, 15.70 mmol) and 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6/catalytic amount) were added and the reaction mixture was stirred vigorously for 16 hours. The reaction mixture was concentrated, the residue was stirred in water (250 ml) and the precipitated solid was filtered off. The solid was dissolved in 1M HCl (150 ml) and the solution washed with ethyl acetate (3×50 ml). The aqueous phase was basified with 2M NaOH and the resultant precipitate was filtered off to give 5-[(1R)-2-amino-1-methylethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine (5.69 g, 100%); NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.88-3.05 (m, 2H), 4.74-4.86 (m, 1H), 5.28 (s, 2H), 7.14-7.25 (m, 2H), 7.30 (d, 1H), 7.33-7.40 (m, 1H), 7.57 (d, 1H), 7.65 (dd, 1H), 7.70 (dt, 1H), 7.87 (dt, 1H), 8.20 (d, 1H), 8.49 (s, 1H), 8.56-8.61 (m, 1H).

Provenance & Evidence