Reacción #45747

Ecuación de reacción

sodium hydrogencarbonate

triethylamine

4-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

(3S)-3-(dimethylamino)pyrrolidine

→

product

Rendimiento 70.3%

4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

Rendimiento 70.3%

Disolventes

ethyl acetate

dimethyl sulfoxide

dimethyl sulfoxide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe solution was gradually heated from room temperature up to 150° C. under nitrogen atmosphere
2. 2
   workup.ADDITIONwas added all at a time
3. 3
   ExtracciónThe aqueous layer was further extracted twice with ethyl acetate
4. 4
   Lavadowashed with saturated brine
5. 5
   Secadodried over anhydrous sodium sulfate
6. 6
   OtroThe insoluble matter was separated by filtration
7. 7
   Otrothe solvent was evaporated away under reduced pressure
8. 8
   Otrothe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=93:7)

Procedimiento

4-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide (I-185) (130 mg, 0.48 mmol) was dissolved in dimethyl sulfoxide (8 ml), then at room temperature, triethylamine (100 μl, 0.48 mmol) was added. The solution was gradually heated from room temperature up to 150° C. under nitrogen atmosphere, a solution of (3S)-3-(dimethylamino)pyrrolidine (79 μl, 0.62 mmol) dissolved in dimethyl sulfoxide (1 ml) was added all at a time. The solution was stirred at the same temperature for 1.25 hours, and the cooled to room temperature. This 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, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=93:7) to obtain a roughly-purified product (124 mg). This was washed with diisopropyl ether to obtain the entitled compound (87 mg, 50%) as a yellow solid.

Fuente