Hydrochloric Acid → N-(2-Fluoro-5-(6-oxo-5-(5-(2-oxopiperazin-1-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

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Reaction Steps

A 10-mL single-neck round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 2h (75 mg, 0.129 mmol), methanol (2 mL) and 4 M HCl in dioxane (2 mL) and the mixture stirred for 2 h. After this time, ethyl acetate (20 mL) and water (20 mL) were added. The pH was adjusted to 6.5 with aqueous 10% potassium carbonate. The aqueous layer was separated and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to a residue which was purified by column chromatography to afford a 56% yield of 21 (40 mg) as a white solid: mp 285-287° C.; 1H NMR (500 MHz, DMSO-d6) δ13.21 (s, 1H), 10.07 (s, 1H), 9.50 (s, 1H), 8.36 (d, 1H, J=2.5 Hz), 8.04 (dd, 1H, J=7.5, 2.0 Hz), 7.71 (s, 1H), 7.70 (m, 1H), 7.65 (m, 1H), 7.53 (d, 1H, =9.0 Hz), 7.41 (t, 1H, J=9.0 Hz), 3.63 (t, 2H, J=5.5 Hz), 3.42 (s, 2H), 3.04 (t, 2H, J=5.0 Hz), 2.78 (t, 2H, J=5.0 Hz), 2.62 (t, 2H, J=5.5 Hz), 1.78 (m, 4H); MS (ESI+) m/z 560.0 (M+H).

Provenance & Evidence