Dimethylformamide → 5-Bromo-3-isopropyl-1H-indole-7-carbonitrile

HRID 1616798Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9](I)[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:12]([CH3:14])[CH3:13].[CH3:15][N:16](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:15]#[N:16])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:12]([CH3:14])[CH3:13]

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of 5-bromo-7-iodo-3-(1-methylethyl)-1H-indole (3.05 g, 8.38 mmol) in DMF (50 mL) was added zinc cyanide (0.52 g, 4.43 mmol) and tetrakis(triphenylphosphine)palladium (0.8 g, 0.692 mmol). The reaction was purged with N2, stirred and heated at 90° C. LCMS indicated that the reaction was complete. The reaction was evaporated to dryness under vacuum. Purification by silica gel chromatography (Analogix, SF25-60 g, 0 to 10% EtOAc in hexanes) and trituration with hexanes, filtering and drying under vacuum gave the product 5-bromo-3-(1-methylethyl)-1H-indole-7-carbonitrile (1.67 g, 6.35 mmol, 76% yield) as a light yellow solid. MS (ES)+ m/e 263.0 [M+H]+.

Workup

customThe reaction was purged with N2
customThe reaction was evaporated to dryness under vacuum
customPurification by silica gel chromatography (Analogix
filtrationSF25-60 g, 0 to 10% EtOAc in hexanes) and trituration with hexanes, filtering
customdrying under vacuum

Sources & evidence

ORD record: ord-e1898d54810a49069529376f9c5d8403
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765792B2

Reaction notes

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