3,8-二氧杂双环[3.2.1]辛烷-2,4-二酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tetrahydrofuran-2,5-dicarboxylic anhydride (1.26 g., 8.8 mmole) and 1-(4-aminobutyl)-4-(6-chloro-2-pyrazinyl)piperazine (2.37 g., 8.8 mmole) were combined and stirred for 30 minutes in 200 ml. of methylene chloride. The solvent was removed in vacuum and replaced with 300 ml. of xylene. The mixture as refluxed for 48 hours with water removal via a Dean-Stark trap. After cooling, the mixture was filtered through 75 g. of silica gel and the column rinsed with 5% ethanol/chloroform. The product was concentrated in vacuum and recrystallized from isopropanol with addition of 4N isopropanolic HCl. 0.60 Grams of the title compound was obtained as the monohydrochloride; m.p. 233°-235° C. (d). The solvent was removed in vacuum The mixture as refluxed for 48 hours with water removal via a Dean-Stark trap After cooling the mixture was filtered through 75 g of silica gel and the column rinsed with 5% ethanol/chloroform The product was concentrated in vacuum recrystallized from isopropanol with addition of 4N isopropanolic HCl

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tetrahydrofuran-2,5-dicarboxylic anhydride (1.5 g., 10 mmole) was dissolved in 150 ml. of toluene in a 500 ml. round bottom flask equipped with a Dean-Stark trap and condenser. 1-(4-Aminobutyl)-4-(2-pyrimidinyl)piperazine (2.59 g., 11 mmole) was added and the mixture was refluxed for 24 hours. When the analysis failed to detect the expected product, the solvent was removed in vacuum and replaced with xylene. Reflux was continued for 48 hours. The solvent was then removed in vacuum and the residue column chromatographed on 100 g. of silica gel using a gradient elution from pure chloroform to 5% ethanol/chloroform. The relevant fractions were combined and concentrated in vacuum and the product crystallized from isopropanol with the addition of 4N HCl/isopropanol. 1.2 Grams of the title compound was obtained as the dihydrochloride; m.p. 221°-222° C. round bottom flask equipped with a Dean-Stark trap and condenser the mixture was refluxed for 24 hours