Acetonitrile → HCID 118071531, compound

HRID 1775452Notes

Reaction equation

HRID 1775452 reaction equation
[F:1][CH:2]([F:22])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[NH:10][C:9]=1[C:18]([NH:20][CH3:21])=[O:19])=[O:4].Cl[CH2:24][C:25]#[N:26].C(#N)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:25]([CH2:24][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:18]([NH:20][CH3:21])=[O:19])=[C:8]2[CH2:7][CH2:6][NH:5][C:3](=[O:4])[CH:2]([F:1])[F:22])#[N:26]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 7856Chloroacetonitrile2×HCID 10796Cesium carbonateHCID 118071484HCID 118071484, compound

Product 1

HCID 118071531HCID 118071531, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-{2-[(difluoroacetyl)amino]ethyl}-5-hydroxy-N-methyl-1H-indole-2-carboxamide (103 mg), chloroacetonitrile (0.0313 mL), and acetonitrile (3.00 mL) were added cesium carbonate (377 mg) and tetrabutylammonium iodide (24.4 mg), followed by stirring at 60° C. for 3 hours. To the mixture was added chloroacetonitrile (0.0209 mL), followed by stirring at 60° C. for 1 hour. To this mixture was added water, followed by extraction with ethyl acetate, the organic layer was washed with saturated brine and subsequently dried over anhydrous sodium sulfate. The insoluble materials were separated by filtration, the filtrate was concentrated under reduced pressure, and then the obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 94:6) to obtain a pale yellow solid. The obtained solid was washed with hexane:ethyl acetate=2:1 to obtain 5-(cyanomethoxy)-3-{2-[(difluoroacetyl)amino]ethyl}-N-methyl-1H-indole-2-carboxamide (5.00 mg) as a pale yellow solid.

Workup

  1. stirringby stirring at 60° C. for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washthe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous sodium sulfate
  5. customThe insoluble materials were separated by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 94:6)
  8. customto obtain a pale yellow solid
  9. washThe obtained solid was washed with hexane

Sources & evidence

ORD record
ord-3f42f6f8842e416ba9722013f8222a27
Source dataset
uspto-grants-2016_02
Patent number
US09260445B2

Reaction notes

Loading…