Diethyl Malonate → Ethyl 5,7-diethyl-4-hydroxy-2-oxo-1,2-dihydro-1,6-naphthyridine-3-carboxylate

HRID 487382Notes

Reaction equation

HRID 487382 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.[NH2:12][C:13]1[CH:18]=[C:17]([CH2:19][CH3:20])[N:16]=[C:15]([CH2:21][CH3:22])[C:14]=1[C:23](OC)=[O:24].[Na]>C(O)C>[CH2:21]([C:15]1[N:16]=[C:17]([CH2:19][CH3:20])[CH:18]=[C:13]2[C:14]=1[C:23]([OH:24])=[C:2]([C:1]([O:9][CH2:10][CH3:11])=[O:8])[C:3](=[O:5])[NH:12]2)[CH3:22]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 5360545SodiumHCID 20094263Methyl 4-amino-2,6-diethylpyridine-3-carboxylate

Product 1

HCID 54684680Ethyl 5,7-diethyl-4-hydroxy-2-oxo-1,2-dihydro-1,6-naphthyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

Diethyl malonate (14.5 ml) and methyl 4-amino-2,6-diethylpyridine-3-carboxylate (21.3 g) was added to a solution of sodium (2.33 g) in ethanol (60 ml) and the resulting mixture was heated at 150° C. for 20 hours in an autoclave. The mixture was allowed to cool and then volatile material was removed by evaporation and the resultant semi-crystalline solid was triturated with ether. The solid was collected by filtration and dissolved in a minimum of water. The solution was acidified with 2M hydrochloric acid and the resulting precipitate was collected by filtration and washed with water. The solid was dried under vacuum to give ethyl 5,7-diethyl-4-hydroxy-2-oxo-1,2-dihydro-1,6-naphthyridine-3-carboxylate (B) (12.72 g); m.p. 240°-242° C.; NMR (CDCl3): 1.34(dt, 6H), 1.52(t, 3H), 2.84(q, 2H), 3.36(q, 2H), 4.52(q, 2H), 6.87(s, 1H), 7.26(s, 1H), 11.41 (broad, 1H); mass spectrum (CI, ammonia): 291 (M+H)+ ; microanalysis, found: C, 62.1; H, 6.2; N, 9.7%; C15H18N2O4 requires: C, 62.1; H, 6.3; N, 9.7%.

Workup

  1. temperatureto cool
  2. customvolatile material was removed by evaporation
  3. customthe resultant semi-crystalline solid was triturated with ether
  4. filtrationThe solid was collected by filtration
  5. dissolutiondissolved in a minimum of water
  6. filtrationthe resulting precipitate was collected by filtration
  7. washwashed with water
  8. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-5eb932e1a8b94c199009f7008acdae2f
Source dataset
uspto-grants-1994_03
Patent number
US05294620

Reaction notes

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