3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hexahydro-1H-isoindole-1,3(2H)-dione (1.0 g, 6.5 mmol) in dry THF (14 mL) was added dropwise to a stirred slurry of LiAlH4 in dry THF (6 mL) at such a rate that the solvent gentle refluxed. The resulting reaction mixture was heated to reflux for 20 h and then allowed to cool to RT. The reaction mixture was cooled with an ice-bath, and H2O (1 mL), a 20% aqueous solution of NaOH (2.5 mL) and H2O (2 mL) were sequentially added. The mixture was filtered and THF removed under reduced pressure. The aqueous phase was extracted with Et2O, and the separated organics were dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (690 mg, 5.52 mmol) as a white powder that was used in the next step without any further purification. The resulting reaction mixture was heated to reflux for 20 h The reaction mixture was cooled with an ice-bath The mixture was filtered THF removed under reduced pressure The aqueous phase was extracted with Et2O the separated organics were dried over Na2SO4 filtered concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of hexahydro-1H-isoindole-1,3(2H)-dione (1.0 g, 6.5 mmol) in dry THF (14 mL) was added dropwise to a stirred slurry of LiAlH4 in dry THF (6 mL) at such a rate that the solvent gentle refluxed. The resulting reaction mixture was heated to reflux for 20 h and then allowed to cool to RT. The reaction mixture was cooled with an ice-bath, and H2O (1 mL), a 20% aqueous solution of NaOH (2.5 mL) and H2O (2 mL) were sequentially added. The mixture was filtered and THF removed under reduced pressure. The aqueous phase was extracted with Et2O, and the separated organics were dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (690 mg, 5.52 mmol) as a white powder that was used in the next step without any further purification. The resulting reaction mixture was heated to reflux for 20 h The reaction mixture was cooled with an ice-bath The mixture was filtered THF removed under reduced pressure The aqueous phase was extracted with Et2O the separated organics were dried over Na2SO4 filtered concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (3aR,7aS)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (3.0 g, 19.9 mmol) and 10% Pd/C (300 mg) in MeOH (100 mL) was shaken in an H2 atmosphere (300 psi) in a Parr apparatus for 24 h. The reaction mixture was filtrated and the liquids concentrated to dryness, affording the title compound (2.6 g, 16.99 mmol), that was sued without any further purification, as a white powder. The reaction mixture was filtrated the liquids concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of cyclohexane-1,2-dicarboximide (6.50 g) in anhydrous dimethylformamide (65 ml), a 60% mineral oil suspension of sodium hydride (1.60 g) was added at room temperature while stirring, and the resultant mixture was continuously stirred for 30 minutes. A solution of 3-[4-(2-pyrimidinyl)piperazinyl]propyl chloride (11.30 g) in anhydrous dimethylformamide (30 ml) was dropwise added thereto, and the resultant mixture was stirred at room temperature for 4.5 hours. The solvent was removed under reduced pressure, and the residue was purified by chromatography to give an oily substance, which was then treated with hydrogen chloride to give N-[3-{4-(2-pyrimidinyl)-1-piperazinyl}propyl]cyclohexane-1,2-dicarboximide hydrochloride. M.P., 180°-182° C. was added at room temperature The solvent was removed under reduced pressure the residue was purified by chromatography to give an oily substance, which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of cyclohexane-1,2-dicarboximide (10 g; 65.3 mmol) in anhydrous dimethylformamide (50 ml), there was added 60% sodium hydride (2.6 g; 68.5 mmol) under nitrogen at room temperature, and the resultant mixture was stirred at the same temperature for 3 hours. Tetramethylene bromide (70.5 g; 0.327 mol) was added thereto, and the mixture was stirred for 3 hours. After completion of the reaction, the resultant mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water twice and with a saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent and excessive tetramethylene bromide were removed by evaporation to give N-(4-bromobutyl)cyclohexane-1,2-dicarboximide. IR νmaxFilm (cm-1): 1770, 1700. After completion of the reaction extracted with ethyl acetate The organic layer was washed with water twice The organic layer was dried over anhydrous magnesium sulfate the solvent and excessive tetramethylene bromide were removed by evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1,2-cyclohexanedicarboxylic anhydride (3 g; 19.5 mmol) and 29% aqueous ammonia (3.4 g) was heated and kept at an inner temperature of 180°-190° C. for 2 hours to give cyclohexane-1,2-dicarboximide. M.P. 132°-136° C. was heated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: