Reaktion #603824
ord-c6c85b89bda342de9a7e2564d038ae9e
Reaktionsgleichung
Edukte
Reagenzien
Reaktionsbedingungen
Aufarbeitung
- 1workup.STIRRINGthe mixture was stirred at 0° C. for 1 hour
- 2Waschenwashed with water and brine
- 3TrocknenThe organic layer was dried over Na2SO4
- 4Sonstigeevaporated to dryness
- 5SonstigeThe crude product was purified by flash chromatography on silica gel (cyclohexane/AcOEt 55:45)
Vorschrift
A solution of N-[3-(4-Bromo-1H-pyrazol-3-yl)-2-fluoro-phenyl]-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (346 mg, 0.726 mmol)(prepared as described in Preparation 1) in anhydrous DMF (4 mL) was cooled to 0° C. under an argon atmosphere and sodium hydride (60% in mineral oil, 87 mg, 2.179 mmol, 3 eq) was added. The mixture was stirred at 0° C. for 30 minutes, then 2-(2-bromo-ethoxy)-tetrahydro-pyran (0.165 mL, 1.089 mmol, 1.5 eq) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was then diluted with AcOEt and washed with water and brine. The organic layer was dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography on silica gel (cyclohexane/AcOEt 55:45) affording 243 mg (55%) of the desired regioisomer N-(3-{4-Bromo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-3-yl}-2-fluoro-phenyl)-2,5-difluoro-N-methoxymethyl-benzenesulfonamide. HPLC (254 nm): Rt: 7.21 min; 1H NMR (DMSO-d6) Shift (selected signals): 8.07 (s, 1H), 7.55-7.69 (m, 2H), 7.47-7.53 (m, 2H), 7.39-7.45 (m, 1H), 7.30-7.35 (m, 1H), 5.09 (s, 2H), 4.51-4.57 (m, 1H), 4.29-4.35 (m, 2H), 3.89-3.97 (m, 1H), 3.70-3.78 (m, 1H), 3.42-3.51 (m, 1H), 3.38 (s, 3H), 1.29-1.69 (3 m, 6H); HRMS (ESI) calcd for C24H26BrF3N3O5S [M+H]+ 604.0723. found 604.0693.