Diisopropylethylamine → Tert-butyl 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl) (methyl)amino]-3-[(methylamino)carbonyl]azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.55 ml, 3.10 mmol) was added to a solution of tert-butyl 3-(methylamino)-3-[(methylamino)carbonyl]azetidine-1-carboxylate (301 mg, 1.24 mmol) in DMF (0.5 ml). After 5 minutes of stirring, the reaction mixture became homogeneous and was warmed up to 85° C. N-(3-chloro-2-fluorophenyl)-6-(chloromethyl)-7-methoxyquinazolin-4-amine (400 mg, 1.03 mmol) was added portionwise over 2 hours. The reaction mixture was cooled to room temperature, diluted with DMF (2 ml) and purified by preparative HPLC (standard basic condition) to afford tert-butyl 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-3[(methylamino)carbonyl]azetidine-1-carboxylate (235 mg, 41%) as a white solid. 1H NMR Spectrum: (CDCl3) 1.45 (s, 9H), 2.34 (s, 3H), 2.90 (d, 3H), 3.78 (brs, 2H), 4.01 (s, 3H), 4.10 (d, 2H), 4.25 (brs, 2H), 6.84 (brs, 1H), 7.17 (m, 2H), 7.29 (s, 1H), 7.60 (brs, 1H), 7.78 (brs, 1H), 8.53 (brs, 1H), 8.75 (s, 1H); Mass Spectrum: (M+H)+ 559.

Provenance & Evidence