Sodium hydride → Tert-butyl 3-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methoxy)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of NaH (271 mg, 60% dispersion in mineral oil, 6.72 mmol) in DMF (2 mL) at 0° C. was added tert-butyl-3-hydroxyazetidine-1-carboxylate (1.0 g, 5.65 mmol). After 30 min, a solution of 403 (1.13 mmol) in DMF (6 mL) and KI (183 mg, 1.13 mmol) were added at 0° C. The reaction mixture was heated to 80° C. for 30 min. The reaction was then quenched by addition of water and the mixture was extracted with AcOEt/MeOH. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified via Biotage [linear gradient 0-10%, (methanol/dichloromethane: SiliaFlash 25 g cartridge]. Title compound 404 was obtained as a beige solid (221 mg, 32% yield for 2 steps). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.71 (s, 1H), 8.62 (d, J=2.4 Hz, 1H), 8.52 (d, J=5.2 Hz, 1H), 8.37 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 7.94 (dd, J=8.0, 2.0 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.23-7.18 (m, 1H), 6.64 (d, J=5.2 Hz, 1H), 6.57 (brd, 1H), 4.53 (s, 2H), 4.42-4.36 (m, 1H), 4.09-4.00 (m, 2H), 3.77-3.68 (m, 2H), 2.59-2.50 (m, 1H), 1.37 (s, 9H), 0.68-0.62 (m, 2H), 0.47-0.41 (m, 2H). MS (m/z): 606.48 (M+H).

Provenance & Evidence