Hydrochloric Acid → HCID 89754176, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2,5-Difluoro-N-[2-fluoro-3-(4-pyridin-4-yl-1H-pyrazol-3-yl)-phenyl]-benzenesulfonamide (200 mg, 0,465 mmol)(prepared as described in Example 15) in anhydrous DMF (4 mL) was added to sodium hydride (60% in mineral oil)(46 mg, 1.162 mmol, 2.5 eq) previously washed with n-hexane under argon atmosphere and cooled to 0° C. After stirring at 0° C. for 40 minutes, freshly prepared 3-oxetanol trifluoromethanesulfonyl ester (144 mg, 0.689 mmol, 1.5 eq) dissolved in dry DMF (1 mL) was added and the mixture was stirred at 0° C. for 1 h. A further addition of sodium hydride (40 mg) and 3-oxetanol trifluoro-methanesulfonyl ester (40 mg) was then made and the reaction mixture was then allowed to warm to room temperature during a night. The reaction mixture was then diluted with water and ethyl acetate. The aqueous phase was brought to pH 4-5 with HCl 2 N and extracted with ethyl acetate. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography on silica gel (ethyl acetate/n-hexane 7:3) affording 24 mg of the title product as a white solid. HPLC (254 nm): Rt: 6.99 min; 1H NMR (DMSO-d6) Shift: 10.68 (br. s., 1H), 8.52 (s, 1H), 8.36-8.40 (m, 2H), 7.51-7.59 (m, 1H), 7.31-7.49 (m, 4H), 721-7.29 (m, 1H), 7.02-7.08 (m, 2H), 5.64 (quip, J=6.9 Hz, 1H), 4.90-5.00 (m, 4H); HRMS (ESI) calcd for C23H18F3N4O3S [M+H]+ 487.1046. found 487.1043.

Provenance & Evidence