Dimethylformamide → 4-Bromo-3-formyl-1H-indole-7-carbonitrile

HRID 2361439Notes

Reaction equation

HRID 2361439 reaction equation
CN([CH:4]=[O:5])C.P(Cl)(Cl)(Cl)=O.[Br:11][C:12]1[CH:20]=[CH:19][C:18]([C:21]([NH2:23])=O)=[C:17]2[C:13]=1[CH:14]=[CH:15][NH:16]2.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[Br:11][C:12]1[CH:20]=[CH:19][C:18]([C:21]#[N:23])=[C:17]2[C:13]=1[C:14]([CH:4]=[O:5])=[CH:15][NH:16]2

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 497579964-Bromo-1H-indole-7-carboxamide

Product 1

HCID 866815304-Bromo-3-formyl-1H-indole-7-carbonitrileYield 65.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of DMF (8.42 mL, 109 mmol) in CH2Cl2(105 mL) stirred on a salt-ice bath was treated dropwise with phosphorus oxychloride (2.57 mL, 27.6 mmol). After 15 min, 4-bromo-1H-indole-7-carboxamide (2 g, 8.37 mmol) was added in one portion while maintaining the temperature below −10° C. After addition, the mixture was stirred at room temperature overnight. After 16 h, ice was added, followed by NaHCO3 and 1 M aqueous NaOH added in portions to make the mixture basic. The mixture was extracted with dichloromethane (3 times), and the combined organic phases were washed with brine, dried and concentrated. The residue was subjected to column chromatography on silica gel (80 g), eluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2, to provide the desired product as a pale solid (1.36 g, 65% yield). LCMS (M+H)+ m/z 248.9, 250.9.

Workup

  1. temperaturewhile maintaining the temperature below −10° C
  2. additionAfter addition
  3. waitAfter 16 h
  4. additionice was added
  5. additionadded in portions
  6. extractionThe mixture was extracted with dichloromethane (3 times)
  7. washthe combined organic phases were washed with brine
  8. customdried
  9. concentrationconcentrated
  10. washeluting with a gradient from 100% CH2Cl2 to 15% Methanol-85% CH2Cl2

Sources & evidence

ORD record
ord-e9c0ab12c17b48bdb0ec94e125fb2421
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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