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

HRID 1253258ノート

反応式

HRID 1253258 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-8e36a806bab64bbc92863294599dd0b0
出典データセット
uspto-grants-1988_05
特許番号
US04748240

反応ノート

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