5-Aminoisoquinoline → 4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-2-(isoquinolin-5-ylhydrazono)-3-oxobutyronitrile

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Reaction Steps

5-Aminoisoquinoline (175 mg, 1.2 mmole) was mixed in 1.5 mL 4 M sulfuric acid in an ice bath. To this mixture was added slowly a 0.3 mL of aqueous solution of NaNO2 (80 mg, 1.16 mmole). The red diazonium solution was then added to the mixture of 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-oxobutyronitrile (200 mg, 0.88 mmole) and NaOAc trihydrate (1.7 g, 12.5 mmole) dissolved in a mixture of 3 mL of acetic acid, 1.5 mL of water and 6 mL of DMF. The resulting brown precipitate was isolated by filtration to give 281 mg of 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-2-(isoquinolin-5-ylhydrazono)-3-oxobutyronitrile, in the form of a salt. The solid was then suspended with NaOAc trihydrate (108 mg, 0.8 mmole) in 24 mL of ethanol and heated to reflux. Excess hydrazine hydrate was added to the mixture in 4 portions (4×36 mg, 2.8 mmole) at intervals of one hour. The suspension became a clear red solution. The solvent was removed in vacuo. The residue was purified by column chromatography (CH2Cl2:MeOH=10:1) to afford a yellow solid. This material was further purified by preparative TLC (CH2Cl2:MeOH:NH3.H2O=200:40:2) to yield 18 mg of the title compound as an orange powder. MS (m/z, ES+): 268 (M+1, 90%).

Provenance & Evidence