反応 #11685

反応方程式

hydrochloric acid

sodium methoxide

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

bromoacetonitrile

→

title compound

収率 26.8%

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

収率 26.8%

溶媒

ethyl acetate

water

tetrahydrofuran

反応条件

後処理

1. 1
   その他After cooing to 0° C.
2. 2
   その他The organic phase was separated
3. 3
   洗浄washed with brine
4. 4
   乾燥dried over anhydrous sodium sulfate
5. 5
   その他After solvent evaporation under vacuum
6. 6
   その他the crude product was purified by reverse phase preparative HPLC

実験手順

(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.

出典