Reaktion #45732

Reaktionsgleichung

sodium hydrogencarbonate

triethylamine

(3S)-3-(dimethylamino)pyrrolidine

2-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

→

product

Ausbeute 85.4%

2-Cyclopropyl-6-(2,3-difluorophenyl)-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-1,3-benzoxazole-4-carbonitrile

Ausbeute 85.4%

Lösungsmittel

ethyl acetate

dimethyl sulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   Sonstigethe reaction liquid
3. 3
   ExtraktionThe aqueous layer was further extracted twice with ethyl acetate
4. 4
   Waschenwashed with saturated brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   SonstigeThe insoluble matter was separated by filtration
7. 7
   Sonstigethe solvent was evaporated away
8. 8
   Sonstigethe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8)

Vorschrift

2-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-177) (109 mg, 0.33 mmol) was dissolved in dimethyl sulfoxide (3 ml), then at room temperature, triethylamine (70 μl, 0.50 mmol) and (3S)-3-(dimethylamino)pyrrolidine (55 μl, 0.43 mmol) were added. The solution was stirred under nitrogen atmosphere at 90° C. for 23 hours. After cooling to room temperature, the reaction liquid was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, then the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8) to obtain a roughly-purified product (119 mg, 85%) as a white solid. This was recrystallized from diisopropyl ether to obtain the entitled compound (71 mg) as a white solid.

Quelle