Water → 2-[4-(Hydroxymethyl)phenyl]-3-phenyl-1,7-naphthyridin-8(7H)-one

HRID 605007Notes

Reaction equation

HRID 605007 reaction equation
[O-][N+:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:8]([C:12]3[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[OH2:26].[OH-].[Na+]>C(OC(=O)C)(=O)C>[OH:19][CH2:18][C:15]1[CH:16]=[CH:17][C:12]([C:8]2[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:6][C:5]3[CH:4]=[CH:3][NH:2][C:11](=[O:26])[C:10]=3[N:9]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 59846139[4-(7-Oxido-3-phenyl-1,7-naphthyridin-2-yl)phenyl]methanol

Product 1

HCID 598461492-[4-(Hydroxymethyl)phenyl]-3-phenyl-1,7-naphthyridin-8(7H)-one

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of [4-(7-oxido-3-phenyl-1,7-naphthyridin-2-yl)phenyl]methanol (144 mg, 0.44 mmol) in acetic anhydride (2 mL) was heated at 130° C. for two hours and then cooled to ˜100° C. Water was added and the stirred mixture was allowed to cool to room temperature. This solution was extracted with methylene chloride and the organic layer was washed with NaHCO3/Na2CO3 solutions, dried, filtered and the solvent evaporated. This residue was determined to be mainly the acylated product, 4-(7-oxo-3-phenyl-7,8-dihydro-1,7-naphthyridin-2-yl)benzyl acetate, by NMR. This material was dissolved in tetrahydrofuran (5 mL) and 5 N NaOH (0.5 mL, 2.5 mmol) was added. The mixture was heated at 60° C. for two hours. The cooled solution was extracted with methylene chloride. The organic layer was washed with aqueous NaHCO3 and then dried, filtered and the solvent evaporated. The residue was purified by column chromatography on silica gel eluting with 0-5% methanol/ethyl acetate (sat'd with ammonia) to give the title compound. 1H-NMR (500 MHz, CDCl3): δ 10.60 (1H, br s), 7.93 (1H, s), 7.44 (2H, d, J=8 Hz), 7.28-7.34 (4H, m), 7.22-7.27 (4H, m), 6.59 (1H, d, J=7 Hz), 4.65 (2H, s). m/e (m+1): 329.2.

Workup

  1. temperaturecooled to ˜100° C
  2. temperatureto cool to room temperature
  3. extractionThis solution was extracted with methylene chloride
  4. washthe organic layer was washed with NaHCO3/Na2CO3 solutions
  5. customdried
  6. filtrationfiltered
  7. customthe solvent evaporated
  8. dissolutionThis material was dissolved in tetrahydrofuran (5 mL)
  9. temperatureThe mixture was heated at 60° C. for two hours
  10. extractionThe cooled solution was extracted with methylene chloride
  11. washThe organic layer was washed with aqueous NaHCO3
  12. customdried
  13. filtrationfiltered
  14. customthe solvent evaporated
  15. customThe residue was purified by column chromatography on silica gel eluting with 0-5% methanol/ethyl acetate (sat'd with ammonia)

Sources & evidence

ORD record
ord-9a5085999e97494dbb04bb94fe78d6a3
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Reaction notes

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