Piperazine → 4-[trans-(2-Hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazoline

HRID 1416450

Reaktionsgleichung

Reaktionsgleichung von HRID 1416450
[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.O1CCOCC1.O>[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

Komponenten

8

Edukt 4

HCID 4837PiperazineHCID 24758Sodium hydrideHCID 225711trans-1,2-CyclopentanediolHCID 2528862,4-Dichloroquinazoline

Produkt 1

HCID 154091264-[trans-(2-Hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazolineAusbeute 34,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Versuchsvorschrift

To a solution of (1R,2R)-cyclopentane-1,2-diol [manufactured by Fluka Co.] (1.16 g) and 2,4-dichloroquinazoline (2.00 g) in dimethylformamide (40 ml) is added gradually 60% sodium hydride (in oil) (0.4 g) with stirring under ice-cooling, and the mixture is stirred at room temperature for 2 hours. The reaction mixture is poured into water and extracted with ethyl acetate twice, and the extract is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform:methanol=100:1, v/v) to give an oily substance. The oily substance thus obtained is dissolved in dioxane (20 ml), and the mixture is slowly added dropwise to a solution of piperazine (1.9 g) in dioxane (20 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for one hour. The reaction mixture is poured into ice-water and extracted with chloroform. The extract is wished with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. The resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform:methanol=20:1, 5:1, v/v) to give 4-[(1R,2R)-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)-quinazoline (1.1 g).

Aufarbeitung

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 2 hours
  3. extractionextracted with ethyl acetate twice
  4. washthe extract is washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated to dryness under reduced pressure
  7. customThe resulting residue is briefly purified with medium pressure column chromatography (eluent, chloroform
  8. custommethanol=100:1, v/v) to give an oily substance
  9. customThe oily substance thus obtained
  10. stirringwith stirring at 70° C.
  11. stirringthe mixture is stirred at the same temperature for one hour
  12. extractionextracted with chloroform
  13. dry with materialdried over anhydrous sodium sulfate
  14. customevaporated to dryness under reduced pressure
  15. customThe resulting residue is purified by medium pressure liquid column chromatography (eluent, chloroform

Quellen und Nachweise

ORD-Eintrag
ord-7d90a691993345f2b7719474e195c330
Quelldatensatz
uspto-grants-1999_06
Patentnummer
US05912247

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