2,2'-[iminobis(ethane-2,1-diyl)]bis(1H-isoindole-1,3(2H)-dione)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromohexylcyanide (1) (13.88 g, 0.073 mol), bis(2-phthalimidoethyl)amine (2) (26.52 g, 0.073 mol), and triethylamine (7.37 g, 0.073 mol) in DMF (120 ml) was heated at 100° C. for 20 hours.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromohexylcyanide (1) (13.88 g, 0.073 mol), bis(2-phthalimidoethyl)amine (2) (26.52 g, 0.073 mol), and triethylamine (7.37 g, 0.073 mol) in DMF (120 ml) was heated at 100° C. for 20 hours.

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

Procedure: To a solution chloroacetyl chloride (1.2 mL, 15.2 mmol) in DCM (65 mL) at 0° C. was added dropwise a solution of 2,2′-(iminodi-2,1-ethanediyl)bis(1H-isoindole-1,3(2H)-dione) (5 g, 13.7 mmol) [prepared according to Anelli, P. L.; et. al. J. Org. Chem. 1984 49, 4197.] and Et3N (2.5 mL, 17.9 mmol) in DCM (65 mL). After 1 h, the solution was partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried (Na2SO4), concentrated and purified via column chromatography (silica, 5% MeOH in DCM (NH4OH)) yielding the title compound (5.9 g, 98%) as a yellow foam: LCMS (ES) m/e 440 (M+H)+. the solution was partitioned between H2O-DCM the aqueous phase was washed several times with DCM The combined organic fractions were dried (Na2SO4) concentrated purified via column chromatography (silica, 5% MeOH in DCM (NH4OH))

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromohexylcyanide (13.88g, 0.073 mol), bis(2-phthalimidoethyl)amine (26.52g, 0.073 mol), and triethylamine (7.37g, 0.073 mol) in DMF (120 ml) was heated at 100° C. for 20 hours. After cooling, the precipitate which had formed was removed by filtration and the filtrate was poured into ice (1000 ml). The aqueous solution was extracted with dichloromethane (3×200 ml). The combined organic extracts were washed with brine and dried over Na2SO4. Removal of the solvent under reduced pressure gave crude product which was chromatographed on silica gel (hexanes - 30% ethyl acetate/hexanes gradient elution). Impure fractions were rechromatographed to provide a total of 14.1g of (6-cyanohexyl)bis(2-phthalimidoethyl)amine (41%) as an oil. The produce was one spot on tlc. The ir spectrum was consistent with the assigned structure. After cooling the precipitate which had formed was removed by filtration the filtrate was poured into ice (1000 ml) The aqueous solution was extracted with dichloromethane (3×200 ml) The combined organic extracts were washed with brine dried over Na2SO4 Removal of the solvent under reduced pressure gave crude product which was chromatographed on silica gel (hexanes - 30% ethyl acetate/hexanes gradient elution) Impure fractions were rechromatographed

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-bromohexylcyanide (1) (13.88 g, 0.073 mol), bis(2-phthalimidoethyl)amine (2) (26.52 g, 0.073 mol), and triethylamine (7.37 g, 0.073 mol) in DMF (120 ml) was heated at 100° C. for 20 hours.