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

HRID 255015Notes

Reaction equation

HRID 255015 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[N:12]([O-])=O.[Na+].[O:16]=[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:26])[N:18]1[CH2:27][C:28](=[O:32])[CH2:29][C:30]#[N:31]>S(=O)(=O)(O)O.C(O)(=O)C.O.CN(C=O)C>[O:16]=[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:26])[N:18]1[CH2:27][C:28](=[O:32])[C:29](=[N:12][NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2)[C:30]#[N:31]

Participants

8

Reactant 3

HCID 707665-AminoisoquinolineHCID 23668193Sodium NitriteHCID 668449574-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-3-oxobutyronitrile

Product 1

HCID 866019704-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-2-(isoquinolin-5-ylhydrazono)-3-oxobutyronitrileYield 83.3%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

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%).

Workup

  1. customThe resulting brown precipitate was isolated by filtration

Sources & evidence

ORD record
ord-bd0997af430a4ec0935a04caaf262495
Source dataset
uspto-grants-2011_01
Patent number
US07875728B2

Reaction notes

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