Hydrochloric Acid → HCID 67416743, compound

Participants

Reaction Steps

To a solution of tert-butyl trans-4-{[4-(cyclopropylethynyl)-9-fluoro-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-6-yl]amino}-3-fluoropiperidine-1-carboxylate (160 mg, 0.324 mmol) in THF (5 mL) under a nitrogen atmosphere was added HCl (4.0 M in 1,4-dioxane) (2 mL, 8.0 mmol), and the reaction was left stirring for two days at room temperature. The reaction mixture was then added to a separatory funnel containing 3:1 CHCl3:2-propanol and saturated aqueous NaHCO3. The phases were separated, and the organic layer was washed with water, then brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product mixture was purified by silica gel chromatography (0-10% CH3OH in CH2Cl2), followed by trituration with methanol afforded the title compound 4-(cyclopropylethynyl)-9-fluoro-6-[(trans-3-fluoropiperidin-4-yl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one. LRMS (APCI) calc'd (C22H20F2N4O3) [M+H]+, 395.2; found 395.1. 1H NMR (500 MHz, DMSO-d6) δ 11.51 (d, 1H), 9.57 (dd, 1H), 8.51 (dd, 1H), 8.19 (d, 1H), 7.57 (d, 1H), 7.53 (dt, 1H), 4.80-4.64 (m, 2H), 3.35 (m [under H2O], 1H), 2.97 (d, 1H), 2.55 (t, 2H), 2.12 (m, 1H), 1.56 (m, 1H), 1.50 (m, 1H), 1.15 (m, 1H), 0.89 (m, 2H), 0.72 (m, 2H).

Provenance & Evidence