Pyridine → 1-(4-Chloro-5-(1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea

Participants

Reaction Steps

To a solution of 3-(5-amino-2-chloro-4-fluorophenyl)-1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-1,6-naphthyridin-2(1H)-one (500 mg, 1.20 mmol) and pyridine (140 mg, 1.8 mmol) in DCM (20 mL) was added phenyl isocyanate (215 mg, 1.8 mmol). The mixture was stirred at RT overnight, concentrated, and purified by prep-HPLC separation to give 1-(4-chloro-5-(1-ethyl-7-(1-methylpyrrolidin-3-ylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea (53 mg, 8.4% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.73 (s, 1H), 7.53 (d, J=11.2 Hz, 1H), 7.41 (d, J=7.6 Hz, 2H), 7.28-7.23 (m, 3H), 6.98-6.95 (m, 1H), 6.35 (s, 1H), 4.39 (s, 1H), 4.11-4.09 (m, 2H), 2.77-2.71 (m, 1H), 2.65-2.61 (m, 1H), 2.44-2.36 (m, 2H), 2.26 (s, 3H), 2.23-2.20 (m, 1H), 1.68-1.62 (m, 1H), 1.64 (t, J=7.2 Hz, 3H).

Provenance & Evidence