Hydrochloric Acid → 1-(6-(3,5-Dichloro-4-hydroxyphenyl)-4-((6-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)quinolin-3-yl)ethanone trihydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl (1-(5-((3-acetyl-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl)amino)pyridin-2-yl)pyrrolidin-3-yl)(methyl)carbamate (94 mg, 0.15 mmol) in THF (5 mL) was added water (3 mL) and HCl (6 M in water, 2 mL, 12 mmol). The reaction mixture was heated at 65° C. for 4 h, cooled to room temperature and concentrated. The resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TEA). The residue was dissolved in methanol (5 mL) and HCl (6 M in water, 1.0 mL, 6 mmol) was added. The resultant solution was concentrated to give the desired product (81.2 mg, 85%) as an orange solid. 1H NMR (500 MHz, MeOD) δ 9.32 (s, 1H), 8.32-8.25 (m, 2H), 8.13-8.05 (m, 2H), 8.03-7.97 (m, 1H), 7.37 (s, 2H), 7.22 (d, J=9.1 Hz, 1H), 4.17-4.07 (m, 2H), 4.00-3.90 (m, 2H), 3.86-3.77 (m, 1H), 2.84 (s, 3H), 2.79 (s, 3H), 2.71-2.60 (m, 1H), 2.48-2.38 (m, 1H). ESI MS m/z 522 [C27H25Cl2N5O2+H]+; HPLC 97.5% (AUC), tR=10.00 min.

Provenance & Evidence