Sodium hydride → HCID 19360137, compound

HRID 376875Notes

Reaction equation

HRID 376875 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([NH:10][C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[CH:8][S:7][C:6]=2[CH:17]=1.[H-].[Na+].Cl.[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25]Cl>CN(C)C=O>[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25][N:10]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)[C:9]1[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:17][C:6]=2[S:7][CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 19360161HCID 19360161, compound

Product 1

HCID 19360137HCID 19360137, compoundYield 74.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Fluoro-3-(4-pyridinylamino)benzo[b]thiophene (3.30 g, 13.5 mmol) was added portionwise as a powder to a suspension of sodium hydride (60% oil dispersion, 1.35 g, 33.8 mmol, washed with hexanes) in 50 mL dimethylformamide. After the anion formation was completed, 3-dimethylaminopropyl chloride hydrochloride (2.56 g, 16.2 mmol) was added as a powder and the resultant mixture was stirred at 70-75° C. for two hours. After cooling, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic extract was washed with water and saturated sodium chloride solution and dried (anhydrous magnesium sulfate), filtered and concentrated to 4.6 g of a brown oil. Elution through silica with 10% methanol in dichloromethane via flash column chromatography yielded 3.3 g of a yellow oil. Kugelrohr distillation (210-220°/0.1 mm Hg) yielded 2.8 g of a clear colorless oil which eventually solidified to a white solid, mp 82-84°.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water and saturated sodium chloride solution
  5. dry with materialdried (anhydrous magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated to 4.6 g of a brown oil
  8. washElution through silica with 10% methanol in dichloromethane via flash column chromatography

Sources & evidence

ORD record
ord-6881ebb31ef4455fad50cfedd68857f1
Source dataset
uspto-grants-2000_02
Patent number
US06022880

Reaction notes

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