Sodium hydride → HCID 19890814, compound

HRID 893617Notes

Reaction equation

HRID 893617 reaction equation
[H-].[Na+].[CH3:3][C:4]1[NH:5][C:6]2[C:11]([C:12](=[O:14])[CH:13]=1)=[N:10][CH:9]=[CH:8][CH:7]=2.[H][H].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[C:26]([C:31]([O:33][CH3:34])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:21][CH:20]=1>CN(C)C=O.O>[CH3:3][C:4]1[CH:13]=[C:12]([O:14][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[C:26]([C:31]([O:33][CH3:34])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:21][CH:20]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 11012181Methyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 122991332-methyl-1H-1,5-naphthyridin-4-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 19890814HCID 19890814, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil; 80 mg) was added to a stirred suspension of the 1,5-naphthyridinone (D1) (320 mg) in N,N-dimethylformamide (DMF) (10 ml). The mixture was stirred until evolution of hydrogen had ceased and then a solution of the bromomethyl compound (C1) in DMF (2 ml) was added. Stirring was continued for 16 hours and then water (100 ml) was added. The mixture was extracted with ethyl acetate (3×25 ml) and the extracts were washed with water (25 ml), followed by saturated sodium chloride solution (25 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue purified by flash chromatography, eluting with methanol/dichloromethane (1:19 v/v) to give methyl 4'-[(2-methyl-1,5-naphthyridin-4-yloxy)methyl]biphenyl-2-carboxylate (A1) (244 mg), as an off-white powder, m.p. 132°-134° C. (from ethyl acetate/hexane); NMR (CDCl3): 2.7(s,3H), 3.6(s,3H), 5.5(s, 2H), 6.9(s,1H), 7.3-7.7 (complex m,3H), 7.85(d,1H), 8.3(dd,1H), 8.9(dd,1H); 13C NMR: (benzylic CH2) 70.6 ppm.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×25 ml)
  2. washthe extracts were washed with water (25 ml)
  3. dry with materialdried (MgSO4)
  4. customThe solvent was removed by evaporation
  5. customthe residue purified by flash chromatography
  6. washeluting with methanol/dichloromethane (1:19 v/v)

Sources & evidence

ORD record
ord-ba2edaf2832f45d4b0a2bb47e59592fa
Source dataset
uspto-grants-1992_06
Patent number
US05126344

Reaction notes

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