Sodium Cyanide → 2-Amino-5-cyano-N,3-dimethylbenzamide

Temperature

80 °C

A three-necked 250-mL round bottom flask equipped with a magnetic stirrer, thermocouple and condenser was charged with of 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Reference Example 1) (10.0 g, 41.1 mmol), sodium cyanide (2.26 g, 44.6 mmol, ground prior to use), zinc (0.815 g, 12.3 mmol, 23.6 meq, particle size −200 mesh (−74 μm)) and [1,1′-bis(diphenylphosphino)ferrocene][(1,2,5,6)-1,5-cyclooctadiene]nickel (prepared by the method of Reference Example 2) (0.297 g, 0.41 mmol) under a nitrogen atmosphere in a glovebox. The flask was removed from the glovebox and swept with nitrogen for 1 h, after which time oxygen-free acetonitrile (48 mL) was added by syringe. The reaction mixture was heated at 80° C. for about 3 h. After 3 h, HPLC analysis of the reaction mixture indicated complete conversion of the 2-amino-5-bromo-N,3-dimethylbenzamide with 2-amino-5-cyano-N,3-dimethylbenzamide being the major product and 2-amino-N,3-dimethylbenzamide a minor product (molar ratio 98.5 to 1.5). Toluene (55 mL) was added to the reaction mixture, and most of the acetonitrile solvent was removed by distillation at atmospheric pressure (67 mL of distillate boiling at 80-82° C. was collected). Toluene (20 mL) and water (20 mL) were added to the concentrated reaction mixture, and the mixture was heated at reflux for 1.5 h, and then cooled to room temperature and filtered. The solid collected was washed with water (90 mL) and dried under vacuum at 45° C. to give the title compound as an off-white powder (7.96 g, 91.4% purity by HPLC, 93.4% yield).

1. customA three-necked 250-mL round bottom flask equipped with a magnetic stirrer
2. customprepared by the method of Reference Example 2) (0.297 g, 0.41 mmol) under a nitrogen atmosphere in a glovebox
3. customThe flask was removed from the glovebox
4. additionafter which time oxygen-free acetonitrile (48 mL) was added by syringe
5. waitAfter 3 h
6. additionToluene (55 mL) was added to the reaction mixture
7. custommost of the acetonitrile solvent was removed by distillation at atmospheric pressure (67 mL of distillate boiling at 80-82° C. was collected)
8. additionToluene (20 mL) and water (20 mL) were added to the concentrated reaction mixture
9. temperaturethe mixture was heated
10. temperatureat reflux for 1.5 h
11. temperaturecooled to room temperature
12. filtrationfiltered
13. customThe solid collected
14. washwas washed with water (90 mL)
15. customdried under vacuum at 45° C.

ORD record

ord-c4fcb0ff73e042d8827d7655339b18ce

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08212075B2