Diisopropylethylamine → Tert-butyl 3-(4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamoyl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (440 mg, 1 mmol) (as prepared in Example 9) and 1-(tert-butoxycarbonyl) azetidine-3-carboxylic acid (402 mg, 2 mmol) in DMF (5 mL) was added HATU (1.1 g, 3 mmol), followed by DIEA (516 mg, 4 mmol). The mixture was sparged with nitrogen and then stirred 50° C. overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column on a silica gel chromatography to give tert-butyl 3-(4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamoyl)azetidine-1-carboxylate (250 mg, 40% yield). 1H-NMR (400 MHz, DMSO-d6): δ 11.01 (s, 1H), 10.72 (s, 1H), 9.79 (s, 1H), 8.19 (d, J=5.6 Hz, 1H), 8.10-8.05 (m, 1H), 7.66 (s, 1H), 7.58-7.53 (m, 3H), 7.14 (t, J=8.8 Hz, 2H), 6.77-6.75 (m, 1H), 3.90-3.84 (m, 4H), 3.55-5.53 (m, 1H), 1.63-1.53 (m, 4H), 1.33 (s, 9H).

Provenance & Evidence