Piperazine → HCID 54489989, compound

HRID 1416460Notes

Reaction equation

HRID 1416460 reaction equation
[CH2:1]1[O:7][CH2:6][C@@H:4]([OH:5])[C@@H:2]1[OH:3].C1OC[C@H](O)[C@H]1O.Cl[C:16]1[N:25]=[C:24](Cl)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1.[H-].[Na+].[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]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:24]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[C:16]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[N:25]=1

Participants

9

Reactant 5

HCID 4837PiperazineHCID 24758Sodium hydrideHCID 2528862,4-DichloroquinazolineHCID 641772HCID 641772, compoundHCID 11521071(3R,4R)-Tetrahydro-3,4-furandiol

Product 1

HCID 54489989HCID 54489989, compound

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 1,4-anhydro-D-threitol [prepared from D-threiol (manufactured by Fluka Co.) in the same manner as in the preparation of 1,4-anhydro-L-threitol (cf. J. Am. Chem. Soc., 74, 5336 (1952)] (11.43 g) and 2,4-dichloroquinazoline (16.8 g) in dimethylformamide (78 ml) is added gradually 60% sodium hydride (in oil) (4.39 g) with stirring under ice-cooling, and the mixture is stirred under ice-cooling for 15 minutes and further at room temperature for 30 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] to give a crystalline substance. The crystalline substance is dividedly added to a solution of piperazine (20.7 g) in dioxane (95 ml) with stirring at 55° C., and the mixture is stirred at the same temperature for 30 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 column chromatography (eluent, chloroform:methanol=10:1, 5:1, v/v) to give 4-[(3R,4R)-(4-hydroxytetrahydrofuran-3-yl)oxy]-2-(1-piperazinyl)quinazoline (5.83 g) as crystals. A part thereof is crystallized from ethanol-ether for obtaining the following physical data.

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred under ice-
  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. customto give a crystalline substance
  8. stirringwith stirring at 55° C.
  9. stirringthe mixture is stirred at the same temperature for 30 minutes
  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-035098bdcaba4a68b1e85c0de06251f3
Source dataset
uspto-grants-1999_06
Patent number
US05912247

Reaction notes

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