1,3-Cyclopentanedicarboxylic anhydride → 3-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione

HRID 1253258

Reaktionsgleichung

Reaktionsgleichung von HRID 1253258
[CH:1]12[C:9](=[O:10])[O:8][C:6](=O)[CH:3]([CH2:4][CH2:5]1)[CH2:2]2.[NH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:18][CH2:17]1>ClCCl>[N:23]1[CH:24]=[CH:25][CH:26]=[N:27][C:22]=1[N:19]1[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][CH2:13][CH2:12][N:11]2[C:6](=[O:8])[CH:3]3[CH2:2][CH:1]([CH2:5][CH2:4]3)[C:9]2=[O:10])[CH2:17][CH2:18]1

Komponenten

4

Edukt 2

HCID 2397991,3-Cyclopentanedicarboxylic anhydrideHCID 128407054-(2-Pyrimidinyl)-1-piperazinebutanamine

Produkt 1

HCID 141563553-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1,3-Cyclopentanedicarboxylic acid (4.0 g., 25 mmole) was converted to the anhydride by refluxing for 3 hours in 20 ml. of acetic anhydride. After removal of excess acetic anhydride, extraction with hexane and evaporation of the hexane, 3.95 g. of cyclopentane-1,3-dicarboxylic anhydride was obtained. The anhydride was combined with 6.51 g. (27 mmole) of 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine in 50 ml. of dichloromethane and stirred at room temperature overnight. The dichloromethane was removed in vacuo and replaced with 75 ml. of toluene. The mixture was refluxed for 24 hours with water separation via a Dean-Stark trap. The product was concentrated under vacuum and chromatographed on 200 g. of silica gel with 5% ethanol/chloroform. The product-containing fractions were combined and concentrated and the residue crystallized (2 crops) from isopropanol with addition of 4N HCl/isopropanol. A second recrystallization from isopropanol gave 1.1 g. of the title compound as the dihydrochloride, hemihydrate; m.p. 201°-203° C.(d).

Aufarbeitung

  1. customThe dichloromethane was removed in vacuo
  2. temperatureThe mixture was refluxed for 24 hours with water separation via a Dean-Stark trap
  3. concentrationThe product was concentrated under vacuum
  4. customchromatographed on 200 g
  5. concentrationconcentrated
  6. customthe residue crystallized (2 crops) from isopropanol
  7. additionwith addition of 4N HCl/isopropanol
  8. customA second recrystallization from isopropanol
  9. customgave 1.1 g

Quellen und Nachweise

ORD-Eintrag
ord-8e36a806bab64bbc92863294599dd0b0
Quelldatensatz
uspto-grants-1988_05
Patentnummer
US04748240

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