5-Hydroxyindole → 6-Amino-4-(1H-5-indolyloxy)nicotinonitrile

HRID 2376920Notes

Reaction equation

HRID 2376920 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[NH2:13][C:14]1[CH:19]=[C:18](Cl)[C:17]([C:21]#[N:22])=[CH:16][N:15]=1>CS(C)=O>[NH2:13][C:14]1[CH:19]=[C:18]([O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)[C:17]([C:21]#[N:22])=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 160545-HydroxyindoleHCID 24758Sodium hydrideHCID 219492196-Amino-4-chloro-3-pyridinecarbonitrile

Product 1

HCID 219493966-Amino-4-(1H-5-indolyloxy)nicotinonitrileYield 59%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

5-Hydroxyindole (313 mg, 2.35 mmol) was dissolved in dimethyl sulfoxide (3 ml); and sodium hydride (90 mg, 2.25 mmol) was gradually added thereto while stirring at room temperature. After the reaction mixture was stirred for 1 hour, 2-amino-4-chloro-5-cyanopyridine (300 mg, 1.96 mmol) synthesized in Production example 215-3 was added thereto; and the reaction mixture was heated and stirred at 120° C. for 4 hours. After allowing to be cooled to room temperature, the reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was distilled off; the residue was subjected to silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol); fractions containing the desired compound was concentrated under reduced pressure; ether was added thereto; and the solid was filtered off, and dried under reduced pressure to yield the title compound (95 mg, 0.38 mmol, 59%).

Workup

  1. stirringAfter the reaction mixture was stirred for 1 hour
  2. additionwas added
  3. temperatureand the reaction mixture was heated
  4. stirringstirred at 120° C. for 4 hours
  5. temperatureto be cooled to room temperature
  6. customthe reaction mixture was partitioned between ethyl acetate and water
  7. washand the organic layer was washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off
  10. additionfractions containing the desired compound
  11. concentrationwas concentrated under reduced pressure
  12. additionether was added
  13. filtrationand the solid was filtered off
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-64cc64276cf84b8f86813df0dc14550a
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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