반응 #45732

반응 방정식

sodium hydrogencarbonate

triethylamine

(3S)-3-(dimethylamino)pyrrolidine

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

→

product

수율 85.4%

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

수율 85.4%

용매

ethyl acetate

dimethyl sulfoxide

반응 조건

후처리

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

실험 절차

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.

출처