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

HRID 1045901

Reaktionsgleichung

Reaktionsgleichung von HRID 1045901
[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

Komponenten

6

Edukt 3

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

Produkt 1

HCID 575169132-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamideAusbeute 16,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1df6df3868b54581b5373a5c39c56146
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569298B2

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