Hydrochloric Acid → HCID 86693846, compound

Participants

Reaction Steps

To a solution of N-{3-[4-(2-cyano-pyridin-4-yl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (60 mg, 0.103 mmol) in dioxane (2 mL) concentrated HCl was added (0.5 mL) and the mixture was stirred at room temperature overnight. After two more additions of concentrated HCl (0.5 mL each) and 5 more hours of stirring, the reaction mixture was diluted with water and neutralized with 32% NaOH. It was then extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure, A 1.1 mixture of the title product and 4-[3-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]pyridine-2-carboxamide was obtained. The two products were separated by flash chromatography on silica gel (gradient cyclohexane/AcOEt 2:8 to pure AcOEt), giving 21 mg of the title compound and 15 mg of 4-[3-(3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]pyridine-2-carboxamide as white solids. HPLC (254 nm): Rt: 6.26 min; 1H NMR (DMSO-d6) Shift: 10.67 (s, 1H), 8.59 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 7.80 (s, 1H), 7.62-7.51 (m, 1H), 7.51-7.43 (m, 1H), 7.43-7.31 (m, 3H), 7.31-7.22 (m, 2H), 4.58-4.36 (m, 1H), 3.98 (dd, J=3.0, 11.7 Hz, 2H), 3.58-3.41 (m, 2H), 2.16-2.04 (m, 2H), 2.04-1.84 (m, 2H); HRMS (ESI) calcd for C26H21F3N5O3S [M+H]+ 540.1312. found 540.1332.

Provenance & Evidence