反应详情

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 6N HCl (2.17 mL, 13.02 mmol) and evaporated to dryness under vacuum. Dried under vacuum overnight. The remaining 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, SF25-60g, 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.

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 remaining 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, SF25-60g, 0 to 15% CH2Cl2/20% (5% NH4OH in MeOH) in CH2Cl2)
16. customevaporated to dryness
17. customtriturated with hexanes
18. customdried under vacuum