반응 #59410

반응 방정식

hydrochloric acid

sodium methoxide

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

bromoacetonitrile

→

title compound

수율 26.8%

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

수율 26.8%

용매

ethyl acetate

water

tetrahydrofuran

반응 조건

후처리

1. 1
   기타After cooing to 0° C.
2. 2
   기타The organic phase was separated
3. 3
   세척washed with brine
4. 4
   건조dried over anhydrous sodium sulfate
5. 5
   기타After solvent evaporation under vacuum
6. 6
   기타the crude product was purified by reverse phase preparative HPLC

실험 절차

(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.

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