Reacción #45860

Ecuación de reacción

(3S)-3-(methylamino)pyrrolidine

dimethyl sulfoxide

2-cyclopropyl-7-fluoro-5-fluoromethyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

triethylamine

→

compound

Rendimiento 24.0%

2-Cyclopropyl-5-fluoromethyl-7-[(3S)-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-4-carbonitrile

Rendimiento 24.0%

Disolventes

brine

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling
2. 2
   Extracciónthe mixture liquid was extracted with ethyl acetate
3. 3
   LavadoNext, the combined organic layer was washed with saturated brine
4. 4
   Secadodried over anhydrous magnesium sulfate
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónthe filtrate was concentrated under reduced pressure
7. 7
   OtroThe resulting residue was purified by middle-pressure liquid chromatography (eluent, dichloromethane
8. 8
   Otromethanol=5:1, v/v) to obtain a crude product of the entitled compound
9. 9
   Lavadowashed with an aqueous saturated sodium hydrogencarbonate solution
10. 10
    Extracciónthe aqueous layer was extracted with ethyl acetate
11. 11
    SecadoThe combined organic layer was dried over anhydrous magnesium sulfate
12. 12
    Filtraciónfiltered
13. 13
    Concentraciónthe filtrate was concentrated under reduced pressure

Procedimiento

Under nitrogen atmosphere at 130° C., (3S)-3-(methylamino)pyrrolidine (85 μl, 801 μmol) was added to a dimethyl sulfoxide (7 ml) solution of 2-cyclopropyl-7-fluoro-5-fluoromethyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-293) (207 mg, 667 μmol) and triethylamine (121 μl, 867 μmol), followed by stirring at the same temperature for 30 minutes. After cooling, saturated brine was added to the reaction liquid, and the mixture liquid was extracted with ethyl acetate. Next, the combined organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by middle-pressure liquid chromatography (eluent, dichloromethane:methanol=5:1, v/v) to obtain a crude product of the entitled compound. The crude product of the entitled compound was dissolved in ethyl acetate, washed with an aqueous saturated sodium hydrogencarbonate solution, then the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the entitled compound (62 mg, 24%) as an amorphous substance.

Fuente