5-Bromo-3-methyl-2-pyridin-3-yl-1H-indole → 3-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile

HRID 593493Notes

Reaction equation

HRID 593493 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)=[C:5]2[CH3:17].[Cu][C:19]#[N:20]>>[CH3:17][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:19]#[N:20])[CH:3]=2)[NH:7][C:6]=1[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

3

Reactant 2

HCID 212605715-Bromo-3-methyl-2-pyridin-3-yl-1H-indoleHCID 178418546HCID 178418546, compound

Product 1

HCID 445541323-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile

Conditions

Temperature
200 °C

Procedure

5-Bromo-3-methyl-2-pyridin-3-yl-1H-indole (5.0 g, 16.7 mmol) and copper (I) cyanide (1.9 g, 20.1 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 200° C. under N2 with vigorous stirring overnight. The mixture is cooled to room temperature and dichloromethane (200 mL) is added. The mixture is filtered through a pad of celite. The filtrate is washed with 10% aqueous ammonia in saturated aqueous ammonium chloride. The aqueous phase is extracted with dichloromethane. 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 3-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.45 (s, 3H), 7.45-7.60 (m, 3H), 8.06-8.11 (m, 1H), 8.15 (s, 1H), 8.60 (dd, J=4.8, 1.5 Hz, 1H), 8.91 (d, J=1.5 Hz, 1H), 11.94 (br. s., 1H). HRMS (ESI) m/z 234.1031 [(M+H)+ Calcd for C15H11N3, 234.1031].

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. additiondichloromethane (200 mL) is added
  5. filtrationThe mixture is filtered through a pad of celite
  6. washThe filtrate is washed with 10% aqueous ammonia in saturated aqueous ammonium chloride
  7. extractionThe aqueous phase is extracted with dichloromethane
  8. dry with materialThe combined organic phase is dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:0)

Sources & evidence

ORD record
ord-50ae1ebf15894748838c5b57e33f7920
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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