Sodium hydride → HCID 21949098, compound

HRID 2376901Notes

Reaction equation

HRID 2376901 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1.[NH2:13][C:14]1[CH:19]=[C:18](Cl)[CH:17]=[CH:16][N:15]=1>CS(C)=O>[NH:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([O:3][C:18]3[CH:17]=[CH:16][N:15]=[C:14]([NH2:13])[CH:19]=3)[CH:12]=2)[CH:8]=[CH:9]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5245086-HydroxyindoleHCID 5818662-Amino-4-chloropyridine

Product 1

HCID 21949098HCID 21949098, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
160 °C

Procedure

Sodium hydride (1.04 g, 26.0 mmol, 60% in oil) was suspended in dimethyl sulfoxide (2.5 ml); 6-hydroxyindole (3.46 g, 26.0 mmol) and 2-amino-4-chloropyridine (2.57 g, 20.0 mmol, WO 02/332872) were subsequently added thereto at room temperature under nitrogen stream; and the reaction mixture was stirred at 160° C. for 8.5 hours. After cooled down to room temperature, the reaction mixture was partitioned between ethyl acetate (150 ml) and a solvent mixture of aqueous ammonia:water=1:1 (50 ml); the organic layer was washed with a solvent mixture of aqueous ammonia:water=1:1, and with brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate, or ethyl acetate:methanol=93:7); and the obtained crystals were suspended in diethyl ether, filtered off, washed with diethyl ether, and dried to yield the title compound (477 mg, 2.12 mmol, 10.6%) as pale yellow crystals.

Workup

  1. customat room temperature
  2. temperatureAfter cooled down to room temperature
  3. customthe reaction mixture was partitioned between ethyl acetate (150 ml)
  4. additiona solvent mixture of aqueous ammonia
  5. washthe organic layer was washed with a solvent mixture of aqueous ammonia
  6. dry with materialwater=1:1, and with brine, dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate, or ethyl acetate:methanol=93:7)
  9. filtrationfiltered off
  10. washwashed with diethyl ether
  11. customdried

Sources & evidence

ORD record
ord-cd2a3d6e13f049aca2ffca2d51a39c9e
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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