4-Methylpyridine → 2-Amino-5-cyano-N,3-dimethylbenzamide

HRID 888255Notes

Reaction equation

HRID 888255 reaction equation
[C-]#N.[Na+].[NH2:4][C:5]1[C:14]([CH3:15])=[CH:13][C:12](Br)=[CH:11][C:6]=1[C:7]([NH:9][CH3:10])=[O:8].[N:17]1C=CC(C)=C[CH:18]=1>[Cu]I>[NH2:4][C:5]1[C:14]([CH3:15])=[CH:13][C:12]([C:18]#[N:17])=[CH:11][C:6]=1[C:7]([NH:9][CH3:10])=[O:8]

Participants

5

Reactant 3

HCID 79634-MethylpyridineHCID 8929Sodium CyanideHCID 442275752-amino-5-bromo-N,3-dimethylbenzamide

Product 1

HCID 251572822-Amino-5-cyano-N,3-dimethylbenzamide

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
155 °C

Procedure

A 250-mL, four-necked flask equipped with a mechanical stirrer and condenser was charged with copper(I) iodide (1.97 g, 10.3 mmol), sodium cyanide (95% purity, 3.30 g, 64.0 mmol), 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Reference Example 1) (10.0 g, 40.9 mmol), 4-picoline (distilled prior to use) (1.16 g, 12.5 mmol) and oxygen-free anisole (20 mL), and then purged with nitrogen, after which time the reaction mixture was maintained under a nitrogen atmosphere. The reaction mixture was heated at about 155° C. for 12 h and then allowed to cool to room temperature overnight. Toluene (20 mL) was added to the solid-containing reaction mixture, the mixture was heated at about 100° C., and then water (60 mL) was added over 20 minutes with stirring. The reaction mixture was stirred for 1 h at 85° C., cooled to room temperature, and then filtered. The solid collected was washed with water (3×mL) and toluene (1×20 mL), and then dried in a vacuum-oven at 55° C. to give the title compound as an off-white solid (7.34 g).

Workup

  1. customA 250-mL, four-necked flask equipped with a mechanical stirrer and condenser
  2. distillationdistilled
  3. customto use) (1.16 g, 12.5 mmol) and oxygen-free anisole (20 mL), and then purged with nitrogen
  4. temperatureafter which time the reaction mixture was maintained under a nitrogen atmosphere
  5. temperatureto cool to room temperature overnight
  6. additionToluene (20 mL) was added to the solid-containing reaction mixture
  7. temperaturethe mixture was heated at about 100° C.
  8. additionwater (60 mL) was added over 20 minutes
  9. stirringThe reaction mixture was stirred for 1 h at 85° C.
  10. temperaturecooled to room temperature
  11. filtrationfiltered
  12. customThe solid collected
  13. washwas washed with water (3×mL) and toluene (1×20 mL)
  14. customdried in a vacuum-oven at 55° C.

Sources & evidence

ORD record
ord-2eafd6b7f2a546a0a37e6c5eb8beaa9f
Source dataset
uspto-grants-2012_08
Patent number
US08247570B2

Reaction notes

Loading…