Dichloromethane → 1-Bromo-6,7-dimethoxyisoquinoline-4-carbonitrile

HRID 1822762Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=O)[NH:8][CH:7]=[C:6]2[C:16]#[N:17].P(Br)(Br)([Br:20])=O.C(Cl)Cl>C1(OC)C=CC=CC=1>[Br:20][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[C:12]([O:13][CH3:14])[CH:11]=2)[C:6]([C:16]#[N:17])=[CH:7][N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The mixture of 6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carbonitrile (8 g, 35 mmol) and phosphorus oxybromide (70 g, 244 mmol) in anisole (30 mL) was heated to 80° C. for 12 h. The solvent and excess POBr3 were removed by rotary evaporator. The resulting solid was washed with hexane and dried. The solid was slowly added to ice and the product was extracted with chloroform. The organic layer was washed with saturated aqueous sodium carbonate solution, saturated aqueous sodium chloride solution (20 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to afford a brown solid. Flash chromatography (Merck Silica gel 60, 70–230 mesh, methylenechloride) afforded 1-bromo-6,7-dimethoxy-isoquinoline-4-carbonitrile (7.5 g, 75%) as a brown solid. LC-MS m/e calcd for C12H9BrN2O2 (MH+) 293. found 293.

Workup

customThe solvent and excess POBr3 were removed by rotary evaporator
washThe resulting solid was washed with hexane
customdried
additionThe solid was slowly added to ice
extractionthe product was extracted with chloroform
washThe organic layer was washed with saturated aqueous sodium carbonate solution, saturated aqueous sodium chloride solution (20 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customto afford a brown solid

Sources & evidence

ORD record: ord-c8df8ddeb91f4a9a865268fe78e05b12
Source dataset: uspto-grants-2006_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07037924B2

Reaction notes

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