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

HRID 1416445

反応式

HRID 1416445 の反応式
[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

参加物

8

反応物 4

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

生成物 1

HCID 154091264-[trans-(2-Hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazoline収率 19.1%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒2 回

実験手順

To a solution of trans-1,2-cyclopentanediol [manufactured by Aldrich Co., cf. J. Chem. Soc., 4026 (1952)] (5.39 g) and 2,4-dichloroquinazoline [cf. J. Am. Chem. Soc., 53, 3867 (1931)] (9.58 g) in dimethylformamide (50 ml) is added gradually 60% sodium hydride (in oil) (2.49 g) 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 6 times. The resulting ethyl acetate solution is dried over anhydrous magnesium sulfate and is evaporated to dryness under reduced pressure, and the residue is briefly purified with medium pressure liquid column chromatography (eluent, chloroform) to give an oily substance. The oily substance thus obtained is dissolved in dioxane (27 ml), and the mixture is slowly added dropwise to a solution of piperazine (9.67 g) in dioxane (36 ml) with stirring at 70° C., and the mixture is stirred at the same temperature for one hour and 10 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 washed with acetone, and the resulting crystals are recrystallized from acetone to give 4-[trans-(2-hydroxycyclopentan-1-yl)oxy]-2-(1-piperazinyl)quinazoline (2.89 g) as crystals.

後処理

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 1 hour and 20 minutes
  3. washwashed with water 6 times
  4. dry with materialThe resulting ethyl acetate solution is dried over anhydrous magnesium sulfate
  5. customis evaporated to dryness under reduced pressure
  6. customthe residue is briefly purified with medium pressure liquid 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 one hour and 10 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. washthe residue is washed with acetone
  15. customthe resulting crystals are recrystallized from acetone

出典と根拠

ORDレコード
ord-d1deb4d9f7864ec69fe938358c49aee8
出典データセット
uspto-grants-1999_06
特許番号
US05912247

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