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

HRID 31132

Reaction equation

HRID 31132 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@H:14]1[CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][C:15]1=[O:24])=[O:12])=[CH:5]2.C[O-].[Na+].Br[CH2:29][C:30]#[N:31].Cl>O1CCCC1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@H:14]1[CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:29][C:30]#[N:31])[C:15]1=[O:24])=[O:12])=[CH:5]2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11534BromoacetonitrileHCID 10942334Sodium MethoxideHCID 44357926(S)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

Product 1

HCID 87730389(S)-3-(5-chloroindole-2-carbonylamino)-1-cyanomethyl-3,4-dihydrocarbostyrilYield 26.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(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.

Workup

  1. customAfter cooing to 0° C.
  2. customThe organic phase was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customAfter solvent evaporation under vacuum
  6. customthe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-5f52219d11a3463cbd7e28dea8f852c5
Source dataset
uspto-grants-2008_09
Patent number
US07425550B2

Linked notes

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