Piperazine → HCID 56991092, compound

HRID 1416466Notes

Reaction equation

HRID 1416466 reaction equation
[C:1]([O:4][C@@H:5]1[CH2:9][C@H:8]([OH:10])[CH:7]=[CH:6]1)(=[O:3])[CH3:2].Cl[C:12]1[N:21]=[C:20](Cl)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1.CC(C)([O-])C.[K+].[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>O1CCCC1.C(OCC)(=O)C.O1CCOCC1>[C:1]([O:4][C@@H:5]1[CH2:9][C@H:8]([O:10][C:20]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[N:21]=2)[CH:7]=[CH:6]1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 4837PiperazineHCID 2528862,4-DichloroquinazolineHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 23665647Potassium tert-butoxide

Product 1

HCID 56991092HCID 56991092, compoundYield 42.5%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (1S,4R)-4-acetoxycyclopent-2-en-1-ol [manufactured by Fluka Co., cf. Tetrahedron, 46, 3155 (1990)] (2.00 g) and 2,4-dichloroquinazoline (2.80 g) in tetrahydrofuran (52 ml) is added potassium t-butoxide (1.90 g) with stirring under ice-cooling, and the mixture is stirred under ice-cooling for 70 minutes. The reaction mixture is diluted with ethyl acetate, and washed with water. 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 an oily substance. The oily substance is dissolved in dioxane (16 ml), and the solution is added dropwise to a solution of piperazine (3.25 g) in dioxane (19 ml) with stirring at 50° C., and the mixture is stirred at the same temperature for 1.5 hour. The reaction mixture is diluted with ethyl acetate and washed with water. The ethyl acetate solution is dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure, and the resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform:methanol=10:1, v/v) to give 4-[(1S,4R)-(4-acetoxycyclopent-2-en-1-yl)oxy]-2-(1-piperazinyl)quinazoline (2.12 g) as oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred under ice-
  3. temperaturecooling for 70 minutes
  4. washwashed with water
  5. dry with materialThe ethyl acetate solution is dried over anhydrous magnesium sulfate
  6. customevaporated to dryness under reduced pressure
  7. customThe resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform)
  8. customto give an oily substance
  9. stirringwith stirring at 50° C.
  10. stirringthe mixture is stirred at the same temperature for 1.5 hour
  11. washwashed with water
  12. dry with materialThe ethyl acetate solution is dried over anhydrous magnesium sulfate
  13. customevaporated to dryness under reduced pressure
  14. customthe resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Sources & evidence

ORD record
ord-966f837c8047477d9bafdd6b4694ac43
Source dataset
uspto-grants-1999_06
Patent number
US05912247

Reaction notes

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