Sodium hydride → 2-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamide

HRID 1045901

Reaction equation

HRID 1045901 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1[C:6]([NH:8][CH3:9])=[O:7].Cl[C:15]1[CH:20]=[C:19]([Cl:21])[N:18]=[CH:17][C:16]=1[C:22]#[N:23]>C1COCC1.CCOC(C)=O>[Cl:21][C:19]1[CH:20]=[C:15]([NH:3][C:4]2[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=2[C:6]([NH:8][CH3:9])=[O:7])[C:16]([C:22]#[N:23])=[CH:17][N:18]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3080722-Amino-N-methylbenzamideHCID 455880804,6-Dichloropyridine-3-carbonitrile

Product 1

HCID 575169132-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamideYield 16.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (2.345 g, 58.64 mmol) was added portionwise to a mixture of 2-amino-N-methylbenzamide (2.201 g, 14.66 mmol), in THF (40 mL) at room temperature under an atmosphere of nitrogen. The resulting suspension was stirred at room temperature for 30 minutes and then 4,6-dichloropyridine-3-carbonitrile (2.536 g, 14.66 mmol) was added portionwise (caution—exotherm and effervescence); the mixture was then heated overnight at 60° C. The mixture was allowed to cool to room temperature and then diluted with EtOAc (200 mL). The mixture was washed sequentially with water (200 mL), water (150 mL), and finally with a saturated solution of NaCl (200 mL). The organic layer was filtered and the residue washed with water followed by EtOAc and then allowed to dry to leave 2-[(2-chloro-5-cyanopyridin-4-yl)amino]-N-methylbenzamide (0.687 g, 16% yield). The filtrate was dried over MgSO4 and then evaporated to leave a solid. The solid was crystallised from MeOH/Et2O to afford a second crop of 2-[(2-chloro-5-cyanopyridin-4-yl)amino]-N-methylbenzamide (2.471 g, 59% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 2.76 (3H, t), 7.10 (1H, d), 7.26-7.32 (1H, m), 7.57 (2H, dd), 7.72-7.74 (1H, m), 8.56 (1H, s), 8.68 (1H, d), 10.63 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=286.98 and 288.94.

Workup

  1. temperaturethe mixture was then heated overnight at 60° C
  2. temperatureto cool to room temperature
  3. washThe mixture was washed sequentially with water (200 mL), water (150 mL)
  4. filtrationThe organic layer was filtered
  5. washthe residue washed with water
  6. customto dry

Sources & evidence

ORD record
ord-1df6df3868b54581b5373a5c39c56146
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Linked notes

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