Reacción #11685

Ecuación de reacción

hydrochloric acid

sodium methoxide

(S)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

bromoacetonitrile

→

title compound

Rendimiento 26.8%

(S)-3-(5-chloroindole-2-carbonylamino)-1-cyanomethyl-3,4-dihydrocarbostyril

Rendimiento 26.8%

Disolventes

ethyl acetate

water

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroAfter cooing to 0° C.
2. 2
   OtroThe organic phase was separated
3. 3
   Lavadowashed with brine
4. 4
   Secadodried over anhydrous sodium sulfate
5. 5
   OtroAfter solvent evaporation under vacuum
6. 6
   Otrothe crude product was purified by reverse phase preparative HPLC

Procedimiento

(S)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 4, 13.4 mg) was dissolved in tetrahydrofuran (5 mL) at room temperature under argon with stirring. After cooing to 0° C., sodium methoxide (4.3 mg) was added, followed 2 h later by bromoacetonitrile (7.2 mg). This was warmed to room temperature over 2 h, and 2 h later water (15 mL), 1.0 M aqueous hydrochloric acid (1 mL), and ethyl acetate (20 mL) were added. The organic phase was separated, washed with brine, and dried over anhydrous sodium sulfate. After solvent evaporation under vacuum, the crude product was purified by reverse phase preparative HPLC to provide the title compound (4 mg). HPLC/MS [M+H]+, 379; HPLC/MS [M+Na]+, 401.

Fuente