Piperazine → HCID 15409124, compound

HRID 1416448Notes

Reaction equation

HRID 1416448 reaction equation
[C@H:1]1([OH:7])[CH2:5][CH2:4][CH2:3][C@@H:2]1[OH:6].Cl[C:9]1[N:18]=[C:17](Cl)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1.[H-].[Na+].[NH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>CN(C)C=O.C(OCC)(=O)C.O1CCOCC1>[OH:6][C@H:2]1[CH2:3][CH2:4][CH2:5][C@@H:1]1[O:7][C:17]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=[C:9]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[N:18]=1

Participants

8

Reactant 4

HCID 4837PiperazineHCID 24758Sodium hydrideHCID 2528862,4-DichloroquinazolineHCID 11400736(1S,2S)-1,2-Cyclopentanediol

Product 1

HCID 15409124HCID 15409124, compoundYield 35.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (1S,2S)-cyclopentane-1,2-diol [manufactured by Fluka Co., cf. J. Org. Chem., 53, 1823 (1988)] (1.00 g) and 2,4-dichloroquinazoline (1.85 g) in dimethylformamide (9 ml) is added gradually 60% sodium hydride (in oil) (409 mg) with stirring under ice-cooling, and the mixture is stirred at room temperature for 1 hour and 20 minutes. The reaction mixture is diluted with ethyl acetate and washed with water 5 times. The resulting ethyl acetate solution is dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure, and the residue is briefly purified with medium pressure column chromatography (eluent, chloroform) to give an oily substance. The oily substance thus obtained is dissolved in dioxane (8 ml), and the mixture is slowly added dropwise to a solution of piperazine (2.21 g) in dioxane (10 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for 40 minutes. The reaction mixture is diluted with ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. The resulting solution is evaporated to dryness under reduced pressure, and the residue is purified by medium pressure liquid column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(1S,2S)-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)-quinazoline (1.03 g) as crystals.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 1 hour and 20 minutes
  3. washwashed with water 5 times
  4. dry with materialThe resulting ethyl acetate solution is dried over anhydrous magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. customthe residue is briefly purified with medium pressure column chromatography (eluent, chloroform)
  7. customto give an oily substance
  8. customThe oily substance thus obtained
  9. stirringwith stirring at 70° C.
  10. stirringthe mixture is stirred at the same temperature for 40 minutes
  11. washwashed with water
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe resulting solution is evaporated to dryness under reduced pressure
  14. customthe residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Sources & evidence

ORD record
ord-7ba66c01524e491294e2a56890f65fd8
Source dataset
uspto-grants-1999_06
Patent number
US05912247

Reaction notes

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