Reaktion #88363

Reaktionsgleichung

propane-1-sulfonic acid [3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide

toluene

diisopropylethylamine

2,6-dichloro-benzoyl chloride

→

desired compound

Ausbeute 36.0%

propane-1-sulfonic acid {3-[5-bromo-1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

Ausbeute 36.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with 200 mL of saturated aqueous sodium bicarbonate
2. 2
   TrocknenThe organic layer is dried over magnesium sulfate
3. 3
   Filtrationfiltered
4. 4
   Einengenthe filtrate concentrated under vacuum
5. 5
   SonstigeThe resulting material is purified by silica gel column chromatography
6. 6
   Wascheneluting with a gradient of ethyl acetate
7. 7
   Sonstigeto provide crude material that
8. 8
   Sonstigeis further purified with additional chromatography
9. 9
   Wascheneluting with 1:1 hexane
10. 10
    Einengenconcentrated under vacuum

Vorschrift

Into a reaction flask under nitrogen, propane-1-sulfonic acid [3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide (9, 8.40 g, 18.3 mmol) is combined with 100 mL of toluene, 4-dimethylaminopyridine (447 mg, 3.7 mmol), diisopropylethylamine (4.74 g, 36.7 mmol) and 2,6-dichloro-benzoyl chloride (10, 4.34 g, 20.7 mmol). The reaction is stirred at room temperature overnight, then diluted with 300 mL of dichloromethane and washed with 200 mL of saturated aqueous sodium bicarbonate, then 200 mL of brine. The organic layer is dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of ethyl acetate:hexane. Appropriate fractions are combined to provide crude material that is further purified with additional chromatography, eluting with 1:1 hexane:dichloromethane up to 100% dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (11, 4.15 g, 36%).

Quelle