Hydrochloric Acid → 6-Methyl-4-(morpholinomethyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 516746Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516746
[O-]CC.[Na+].[C:5]([CH2:7][C:8]([NH2:10])=[O:9])#[N:6].[N:11]1([CH2:17][C:18]#[C:19][C:20](=O)[CH3:21])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.Cl>CCO>[CH3:21][C:20]1[NH:10][C:8](=[O:9])[C:7]([C:5]#[N:6])=[C:18]([CH2:17][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:19]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 7898CyanoacetamideHCID 2723922Sodium ethoxideHCID 674677495-(Morpholin-4-yl)pent-3-yn-2-one

Produkt 1

HCID 674663986-Methyl-4-(morpholinomethyl)-2-oxo-1,2-dihydropyridine-3-carbonitrileAusbeute 32,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel3×

Versuchsvorschrift

To a stirred solution of 21 wt % sodium ethoxide in EtOH (4.2 g, 12.96 mmol) in EtOH (30 mL) was added 2-cyanoacetamide (1.1 g, 13.08 mmol). The reaction was stirred for 15 min. then a solution of 5-(4-morpholinyl)-3-pentyn-2-one (2.0 g, 11.96 mmol) in EtOH was added to the reaction in one portion. (The reaction quickly turned dark red.) The reaction was stirred overnight at RT, neutralized with 6 N HCl (2.17 mL, 13.02 mmol) and evaporated to dryness under vacuum. Dried under vacuum overnight. The reamaining dark solid was triturated with a solution of (9:1) CH2Cl2, MeOH (50 mL), filtered from insoluble material, washed with (9:1) CH2Cl2, MeOH, and the filtrate evaporated to dryness under vacuum. The dark solid was triturated with a solution of (1:1) EtOAc in hexanes, filtered, washed with (1:1) EtOAc in hexanes, and dried under vacuum to give a brown solid (removed a lot of fast running non-polar impurities). The crude product was purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 15% CH2Cl2/20%(5% NH4OH in MeOH) in CH2Cl2). The pure fractions were combined, evaporated to dryness, triturated with hexanes and dried under vacuum to give the product 6-methyl-4-(4-morpholinylmethyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (0.90 g, 3.86 mmol, 32.3% yield) as a light tan solid.

Aufarbeitung

  1. custom(The reaction quickly turned dark red
  2. stirring) The reaction was stirred overnight at RT
  3. customevaporated to dryness under vacuum
  4. customDried under vacuum overnight
  5. customThe reamaining dark solid was triturated with a solution of (9:1) CH2Cl2, MeOH (50 mL)
  6. filtrationfiltered from insoluble material
  7. washwashed with (9:1) CH2Cl2, MeOH
  8. customthe filtrate evaporated to dryness under vacuum
  9. customThe dark solid was triturated with a solution of (1:1) EtOAc in hexanes
  10. filtrationfiltered
  11. washwashed with (1:1) EtOAc in hexanes
  12. customdried under vacuum
  13. customto give a brown solid (
  14. customremoved a lot
  15. customThe crude product was purified by silica gel chromatography (Analogix
  16. customevaporated to dryness
  17. customtriturated with hexanes
  18. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-6c44607474644904b0efdab6b4e6ac99
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09114141B2

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