Piperazine → HCID 22375260, compound

HRID 1416464Notes

Reaction equation

HRID 1416464 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH:3]=[CH:2]1.Cl[C:8]1[N:17]=[C:16](Cl)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.[H-].[Na+].[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>CN(C)C=O.C(OCC)(=O)C.O1CCOCC1>[CH:1]1([O:6][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=[C:8]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:17]=2)[CH2:5][CH2:4][CH:3]=[CH:2]1

Participants

8

Reactant 4

HCID 4837PiperazineHCID 24758Sodium hydrideHCID 2201642-Cyclopentene-1-olHCID 2528862,4-Dichloroquinazoline

Product 1

HCID 22375260HCID 22375260, compoundYield 44.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-cyclopenten-1-ol [cf. J. Org. Chem., 40, 1864 (1975)] (996 mg) and 2,4-dichloroquinazoline (2.36 g) in dimethylformamide (10 ml) is added 60% sodium hydride (in oil) (568 mg) with stirring at room temperature, and the mixture is stirred at room temperature for 2 hours. The reaction mixture is diluted with ethyl acetate, and washed with water 5 times. The ethyl acetate solution is dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. The resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform) to give a crystalline substance. The crystalline substance is added to a solution of piperazine (4.02 g) in dioxane (26 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for one hour. The reaction mixture is diluted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure. The resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(cyclopent-2-en-1-yl)oxy]-2-(1-piperazinyl) quinazoline (1.57 g) as crystals.

Workup

  1. stirringthe mixture is stirred at room temperature for 2 hours
  2. washwashed with water 5 times
  3. dry with materialThe ethyl acetate solution is dried over anhydrous magnesium sulfate
  4. customevaporated to dryness under reduced pressure
  5. customThe resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform)
  6. customto give a crystalline substance
  7. stirringwith stirring at 70° C.
  8. stirringthe mixture is stirred at the same temperature for one hour
  9. washwashed with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated to dryness under reduced pressure
  12. customThe resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Sources & evidence

ORD record
ord-45a0b3bafe354a1d871012c96986c3a9
Source dataset
uspto-grants-1999_06
Patent number
US05912247

Reaction notes

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