Methyl iodide → 1-methyl-1H-indole-5-carbonitrile
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=CC=1)[NH:7]C=[CH:5]2.C([O-])([O-])=O.[K+].[K+].IC.[CH3:19][N:20]1[C:24](=O)[CH2:23][CH2:22][CH2:21]1>CN(C=O)C>[CH3:19][N:20]1[C:24]2[C:23](=[CH:5][C:4]([C:8]#[N:7])=[CH:3][CH:2]=2)[CH:22]=[CH:21]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of 5-bromoindole (500 mg; 2.55 mmol) and cuprous cyanide (342 mg; 3.83 mmol) in NMP (10 mL) was heated under microwave irradiations to 100° C. for 30 minutes then at 200° C. for 30 minutes. The reaction mixture was partitioned with water and DCM and the organic layer was washed with brine and concentrated in vacuo to give a pink solid. Purification by silica column chromatography (DCM) gave a white solid. It was dissolved in DMF (5 mL) and K2CO3 (704 mg; 5.10 mmol) and iodomethane (543 mg; 3.83 mmol) were successively added. The reaction mixture was stirred at RT for 3 days and then partitioned between water and EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated under vacuum to give a slightly yellow oil which crystallized upon standing to give the title compound as an off-white solid (80 mg, 70%). LC/MS (Method A): 156.9 (M+H)+.
Workup
- customThe reaction mixture was partitioned with water and DCM
- washthe organic layer was washed with brine
- concentrationconcentrated in vacuo
- customto give a pink solid
- customPurification by silica column chromatography (DCM)
- customgave a white solid
- custompartitioned between water and EtOAc
- washThe organic layer was washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated under vacuum
- customto give a slightly yellow oil which
- customcrystallized
Sources & evidence
- ORD record
- ord-2d1a23f06efe4132a2780d890867b159
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08741923B2
Reaction notes
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