Sodium hydride → 6-[(3-chloro-4-fluoro-phenyl)methyl]-4-hydroxy-N,N,2-trimethyl-3,5-dioxo-7,8-dihydro-2,6-naphthyridine-1-carboxamide

HRID 1817350Notes

Reaction equation

HRID 1817350 reaction equation
[OH:1][C:2]1[C:3](=[O:19])[N:4]([CH3:18])[C:5]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:26]Br>CN(C=O)C>[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:26][N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[C:2]([OH:1])[C:3](=[O:19])[N:4]([CH3:18])[C:5]=2[C:13]([N:15]([CH3:16])[CH3:17])=[O:14])[C:10]1=[O:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27575424-(Bromomethyl)-2-chloro-1-fluorobenzeneHCID 690584564-hydroxy-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide

Product 1

HCID 546922716-[(3-chloro-4-fluoro-phenyl)methyl]-4-hydroxy-N,N,2-trimethyl-3,5-dioxo-7,8-dihydro-2,6-naphthyridine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Hydroxy-N,N,2-trimethyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxamide (0.43 g, 0.0016 mol) was dissolved in 10 mL dry DMF and 100 mg NaH was added. The mixture was allowed to stir until the bubbles ceased, then 3-chloro-4-fluoro benzyl bromide (0.362 g, 0.0016 mole) was added. The reaction was quenched with 30 mL of a 10% aq KHSO4 solution and diluted with 100 mL chloroform. The reaction was further diluted with 100 mL brine and allowed to stir vigorously for 30 minutes. The layers were separated and the aqueous layer was washed with chloroform. The organic fractions were combined and dried over NaSO4, filtered and concentrated under high vacuum to remove the DMF (yield 0.5 g, 75%). HPLC analysis showed 85% purity. The solid product was crystallized first from isopropanol, then from ethanol.

Workup

  1. customThe reaction was quenched with 30 mL of a 10% aq KHSO4 solution
  2. additiondiluted with 100 mL chloroform
  3. additionThe reaction was further diluted with 100 mL brine
  4. stirringto stir vigorously for 30 minutes
  5. customThe layers were separated
  6. washthe aqueous layer was washed with chloroform
  7. dry with materialdried over NaSO4
  8. filtrationfiltered
  9. concentrationconcentrated under high vacuum
  10. customto remove the DMF (yield 0.5 g, 75%)
  11. customThe solid product was crystallized first from isopropanol

Sources & evidence

ORD record
ord-68f6886a6e9c49e08468f5b522a12126
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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