Reaktion #74177

Reaktionsgleichung

DCM

N-[3-(4-Bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

4-pyridylboronic acid pinacol ester

cesium carbonate

→

N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

Ausbeute 86.0%

Lösungsmittel

dimethoxyethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAr was bubbled through the solution for 5 minutes
2. 2
   workup.ADDITIONWater (0.5 mL) was added
3. 3
   SonstigeThe vial was sealed
4. 4
   Sonstigeirradiated in the microwave oven at 100° C. for 30 minutes
5. 5
   FiltrationThe reaction mixture was then filtered over a Celite pad
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   Waschenwashed with saturated aqueous NaHCO3 and brine
8. 8
   TrocknenThe organic phase was dried over Na2SO4
9. 9
   Sonstigeevaporated to dryness
10. 10
    SonstigeThe crude product was purified by chromatography on silica gel (DCM/MeOH 97:3)

Vorschrift

In a vial suitable for microwave irradiation N-[3-(4-Bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide (288 mg, 0.509 mmol) was dissolved in dimethoxyethane (4.5 mL) and Ar was bubbled through the solution for 5 minutes. Water (0.5 mL) was added, followed by 4-pyridylboronic acid pinacol ester (209 mg, 1.018 mmol, 2 eq), cesium carbonate (497 mg, 1.527 mmol, 3 eq) and Pd(dppf)Cl2.DCM (42 mg, 0.051 mmol, 0.1 eq). The vial was sealed and irradiated in the microwave oven at 100° C. for 30 minutes. The reaction mixture was then filtered over a Celite pad and concentrated under reduced pressure. The residue was taken up with ethyl acetate and washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (DCM/MeOH 97:3) to give 247 mg (86% yield) of N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide as an off-white solid.

Quelle