Reaktion #45730

Reaktionsgleichung

sodium hydrogencarbonate

triethylamine

(3S)-3-(dimethylamino)pyrrolidine

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

→

compound

Ausbeute 16.0%

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

Ausbeute 16.0%

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=96:4)
9. 9
   Sonstigeto obtain a roughly-purified product (211 mg, 74% for 2 steps) as a white solid
10. 10
    SonstigeThis was recrystallized from ethyl acetate and diisopropyl ether

Vorschrift

2-Cyclopropyl-6-(3,5-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-176) (including impurities, estimated as 0.68 mmol) was dissolved in dimethyl sulfoxide (5 ml), then at room temperature, triethylamine (142 μl, 1.02 mmol) and (3S)-3-(dimethylamino)pyrrolidine (112 μl, 0.88 mmol) were added, the solution was stirred under nitrogen atmosphere at 90° C. for 15 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=96:4) to obtain a roughly-purified product (211 mg, 74% for 2 steps) as a white solid. This was recrystallized from ethyl acetate and diisopropyl ether to obtain the entitled compound (46 mg) as a white solid.

Quelle