Methanol → 4-methoxy-6-(4-methoxybenzyl)-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide

HRID 1817348Notes

Reaction equation

HRID 1817348 reaction equation
[OH:1][C:2]1[N:3]=[C:4]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])[C:5]2[CH2:6][CH2:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:9](=[O:14])[C:10]=2[C:11]=1[O:12][CH3:13].[CH3:29][O-].C[O-].[Mg+2].CO.IC>CN(C=O)C>[CH3:13][O:12][C:11]1[C:2](=[O:1])[N:3]([CH3:29])[C:4]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[C:5]2[C:10]=1[C:9](=[O:14])[N:8]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 887MethanolHCID 6328Methyl iodideHCID 164537Methanol, magnesium salt (2:1)HCID 178490769HCID 178490769, compound

Product 1

HCID 690582414-methoxy-6-(4-methoxybenzyl)-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-hydroxy-4-methoxy-6-(4-methoxybenzyl)-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (5.00 g) in DMF (50 mL) was added magnesium methylate (14.3 mL of a 6-10% methanol solution), and the reaction was heated to 50° C. for 1 hour. The reaction was treated with iodomethane (17.66 mL) and allowed to stir at 50 degrees for 1.5 hours. The reaction was quenched with 15 mL 10% aq KHSO4 and concentrated in vacuo to remove the methanol. The mixture was diluted with 300 mL chloroform and the phases were separated. The aqueous layer was washed twice more with chloroform. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The remaining solid was purified on an Isco automated system affixed with a Biotage Flash 40 (L) (120 g) cartridge eluted with 0-10% MeOH in EtOAc over 20 minutes and hold at 10% MeOH for 45 minutes. The product eluted last, pure by HPLC/MS and NMR.

Workup

  1. customThe reaction was quenched with 15 mL 10% aq KHSO4
  2. concentrationconcentrated in vacuo
  3. customto remove the methanol
  4. additionThe mixture was diluted with 300 mL chloroform
  5. customthe phases were separated
  6. washThe aqueous layer was washed twice more with chloroform
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe remaining solid was purified on an Isco automated system
  11. washeluted with 0-10% MeOH in EtOAc over 20 minutes
  12. waithold at 10% MeOH for 45 minutes
  13. washThe product eluted last, pure by HPLC/MS and NMR

Sources & evidence

ORD record
ord-a8e54dc670cd45eb8dc58402ae1083e4
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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