5-bromo-2-pyridin-3-yl-1H-indole → 2-pyridin-3-yl-1H-indole-5-carbonitrile

HRID 1661541Notes

Reaction equation

HRID 1661541 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=[CH:5]2.[Cu][C:18]#[N:19]>>[N:13]1[CH:14]=[CH:15][CH:16]=[C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([C:18]#[N:19])=[CH:10][CH:9]=3)[CH:12]=1

Participants

3

Reactant 2

HCID 670933625-bromo-2-pyridin-3-yl-1H-indoleHCID 178418546HCID 178418546, compound

Product 1

HCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

Conditions

Temperature
160 °C

Procedure

5-Bromo-2-pyridin-3-yl-1H-indole (7.0 g, 21.8 mmol) and copper (I) cyanide (2.3 g, 26.1 mmol) are placed in a round bottom flask which is flushed with N2. N-Methylpyrrolidinone (40 mL) is added via syringe. The resulting mixture is heated to 160° C. under N2 with vigorous stirring overnight. The mixture is cooled to room temperature and poured into 10% aqueous ammonia in saturated aqueous ammonium chloride (300 mL). The aqueous phase is extracted with dichloromethane (100 mL) five times. The combined organic phase is dried over sodium sulfate and concentrated. The residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:0) to give 2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.20 (s, 1H), 7.48 (dd, J=8.3, 1.5 Hz, 1H), 7.51-7.55 (m, 1H), 7.59 (d, J=8.6 Hz, 1H), 8.12 (s, 1H), 8.25-8.29 (m, 1H), 8.56 (dd, J=4.8, 1.5 Hz, 1H), 9.14 (d, J=1.8 Hz, 1H), 12.27 (s, 1H). HRMS (ESI) m/z 220.0869 [(M+H)+ Calcd for C14H9N3, 220.0875].

Workup

  1. customwhich is flushed with N2
  2. additionN-Methylpyrrolidinone (40 mL) is added via syringe
  3. temperatureThe mixture is cooled to room temperature
  4. additionpoured into 10% aqueous ammonia in saturated aqueous ammonium chloride (300 mL)
  5. extractionThe aqueous phase is extracted with dichloromethane (100 mL) five times
  6. dry with materialThe combined organic phase is dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:0)

Sources & evidence

ORD record
ord-6f89d26e7b4148289078c761c0e30277
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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