反应详情

The hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-N-methylazetidine-3-carboxamide (110 mg, 0.22 mmol Example 99), formaldehyde (54 μl of a 37% wt aqueous solution, 0.67 mmol) and diisopropylethylamine (78 μl, 0.45 mmol) were stirred at room temperature in 5% acetic acid in 1,2-dichloroethane (2 ml) with 3 Å molecular sieves. Sodium triacetoxyborohydride (95 mg, 0.45 mmol) was added portionwise over 0.5 hours. After 2 hours, the reaction mixture was concentrated under reduced pressure and the residues purified preparative HPLC (standard basic conditions) to give the title product (68 mg, 65%) as a white powder. 1H NMR Spectrum: (CDCl3) 2.40 (s, 3H), 2.45 (m, 3H), 2.89 (s, 3H), 3.39 (brs, 2H), 3.60 (d, 2H), 3.95 (s, 2H), 3.98 (s, 3H), 7.17 (m, 2H), 7.25 (s, 1H), 7.44 (brs, 1H), 7.84 (brs, 1H), 8.00 (s, 1H), 8.51 (brs, 1H), 8.74 (s, 1H); Mass Spectrum: (M+H)+ 473.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. customthe residues purified preparative HPLC (standard basic conditions)