Piperazine → HCID 54489988, compound

HRID 1416457Notes

Reaction equation

HRID 1416457 reaction equation
[CH2:1]1[O:7][CH2:6][C@H:4]([OH:5])[C@H:2]1[OH:3].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:5][C@H:4]1[CH2:6][O:7][CH2:1][C@@H:2]1[O:3][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 641772HCID 641772, compound

Product 1

HCID 54489988HCID 54489988, compoundYield 31.1%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 1,4-anhydro-L-threitol [manufactured by Aldrich Co., cf. J. Am. Chem. Soc., 74, 5336 (1952)] (7.34 g) and 2,4-dichloroquinazoline (5.00 g) in dimethylformamide (42 ml) is added gradually 60% sodium hydride (in oil) (1.92 g) with stirring under ice-cooling, and the mixture is stirred at room temperature for one hour and 10 minutes. 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 by medium pressure liquid column chromatography [eluent, chloroform, (chloroform:methanol=200:1, v/v) ] to give an oily substance. The oily substance is dissolved in dioxane (35 ml), and the mixture is slowly added dropwise to a solution of piperazine (9.61 g) in dioxane (70 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, 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 column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(3S,4S)-(4-hydroxytetrahydrofuran-3-yl)oxy]-2-(1-piperazinyl)quinazoline (2.47 g) as crystals.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for one hour and 10 minutes
  3. washwashed with water 5 times
  4. dry with materialThe ethyl acetate solution is dried over anhydrous magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. customThe resulting residue is briefly purified by medium pressure liquid column chromatography [eluent, chloroform
  7. custom(chloroform:methanol=200:1, v/v) ] to give an oily substance
  8. stirringwith stirring at 50° C.
  9. stirringthe mixture is stirred at the same temperature for 1.5 hour
  10. washwashed with water
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe resulting solution is evaporated to dryness under reduced pressure
  13. customthe residue is purified by medium pressure column chromatography (eluent, chloroform

Sources & evidence

ORD record
ord-0f0f2eed96804a7ba6fd1fe05de5706a
Source dataset
uspto-grants-1999_06
Patent number
US05912247

Reaction notes

Loading…