Sodium hydride → HCID 10270596, compound

HRID 2215310Notes

Reaction equation

HRID 2215310 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:20]=[C:21]([Cl:23])[CH:22]=1)[O:7][C:8]1[C:9]([CH2:18][CH3:19])=[N:10][N:11]([CH2:15][CH2:16][OH:17])[C:12]=1[CH2:13][CH3:14].Cl.Cl[CH2:26][CH2:27][NH2:28]>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:20]=[C:21]([Cl:23])[CH:22]=1)[O:7][C:8]1[C:9]([CH2:18][CH3:19])=[N:10][N:11]([CH2:15][CH2:16][O:17][CH2:26][CH2:27][NH2:28])[C:12]=1[CH2:13][CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 97937372-Chloroethylamine hydrochloride2×HCID 9967239HCID 9967239, compound

Product 1

HCID 10270596HCID 10270596, compoundYield 18.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in oil, 24 mg, 0.600 mmol) was added to a stirred solution of the pyrazole of Example 2 (100 mg, 0.303 mmol) in dry N,N-dimethylformamide (4 ml) at 0° C. under nitrogen. The mixture was stirred at 0° C. for 30 minutes and 2-chloroethylamine hydrochloride (53 mg, 0.455 mmol) was added. The reaction mixture was stirred at 0° C. for 30 minutes and then stirred at room temperature for 30 minutes. The reaction was cooled to 0° C., further sodium hydride (60% dispersion in oil, 24 mg, 0.600 mmol) and 2-chloroethylamine hydrochloride (53 mg, 0.455 mmol) were added and the reaction was stirred for 1 hour. The reaction was quenched by the addition of water (5 ml) and extracted with ether (10 ml). The organic layer was washed with 2M aqueous hydrochloric acid (30 ml). The acid was neutralised with solid sodium carbonate and extracted with ether (3×20 ml). The combined ether layers were dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:4:1, by volume) to provide the title compound (21 mg) as a colourless oil.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  2. stirringstirred at room temperature for 30 minutes
  3. temperatureThe reaction was cooled to 0° C.
  4. stirringthe reaction was stirred for 1 hour
  5. customThe reaction was quenched by the addition of water (5 ml)
  6. extractionextracted with ether (10 ml)
  7. washThe organic layer was washed with 2M aqueous hydrochloric acid (30 ml)
  8. extractionextracted with ether (3×20 ml)
  9. dry with materialThe combined ether layers were dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:4:1, by volume)

Sources & evidence

ORD record
ord-2abd6fb7954b40d7806b94c2ef128fad
Source dataset
uspto-grants-2006_09
Patent number
US07109228B2

Reaction notes

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