Sodium hydride → 2-[(2-chloro-5-cyanopyridin-4-yl)amino]-N-methoxy-N-methylbenzamide

HRID 1045902Notes

Reaction equation

HRID 1045902 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7].Cl[C:17]1[CH:22]=[C:21]([Cl:23])[N:20]=[CH:19][C:18]=1[C:24]#[N:25]>C1COCC1.CCOC(C)=O>[Cl:23][C:21]1[CH:22]=[C:17]([NH:3][C:4]2[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=2[C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])[C:18]([C:24]#[N:25])=[CH:19][N:20]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 110522422-amino-N-methoxy-N-methylbenzamideHCID 455880804,6-Dichloropyridine-3-carbonitrile

Product 1

HCID 866551312-[(2-chloro-5-cyanopyridin-4-yl)amino]-N-methoxy-N-methylbenzamideYield 34.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.888 g, 22.20 mmol) was added portionwise to a mixture of 2-amino-N-methoxy-N-methylbenzamide (1.00 g, 5.55 mmol), in THF (30 mL) cooled to 0° C. under an atmosphere of nitrogen. The resulting suspension was stirred at room temperature for 20 minutes and then 4,6-dichloropyridine-3-carbonitrile (0.960 g, 5.55 mmol) was added portionwise and the mixture heated overnight at 60° C. The mixture was allowed to cool to room temperature and then diluted with EtOAc (50 mL). The mixture was washed sequentially with water (50 mL), a saturated solution of NaHCO3 (50 mL), water (25 mL) and finally with a saturated solution of NaCl (20 mL). The organic layer was dried over Na2SO4 and then evaporated. The residue was crystallised from Et2O/MeOH to afford 2-[(2-chloro-5-cyanopyridin-4-yl)amino]-N-methoxy-N-methylbenzamide (0.602 g, 34% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 3.15 (3H, s), 3.47 (3H, s), 6.56 (1H, s), 7.39-7.44 (2H, m), 7.52-7.56 (2H, m), 8.45 (1H, s), 9.33 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=317.28 and 319.30.

Workup

  1. temperaturethe mixture heated overnight at 60° C
  2. temperatureto cool to room temperature
  3. washThe mixture was washed sequentially with water (50 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. customevaporated
  6. customThe residue was crystallised from Et2O/MeOH

Sources & evidence

ORD record
ord-38b6c115fcc7442a887de649eb347a1c
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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