Hydrochloric Acid → 1-Benzyl-8-cyano-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 919668Notes

Reaction equation

HRID 919668 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:25])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([CH3:24])=[CH:8]2)=[O:4].[C:26]([Cu])#[N:27].Cl>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:25])=[C:7]2[C:12](=[C:13]([C:26]#[N:27])[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([CH3:24])=[CH:8]2)=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 867141041-Benzyl-8-bromo-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 682975501-Benzyl-8-cyano-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 69.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-benzyl-8-bromo-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (164 mg, 0.41 mmol) and CuCN (73 mg, 0.82 mmol) was refluxed for 35 min under nitrogen atmosphere. After the mixture was cooled to r.t., CH2Cl2 (100 mL) was added. 4M HCl was added with stirring until no more solid was present. The aqueous layer was extracted with additional CH2Cl2, and the combined organic layer was dried over MgSO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-100% EtOAc/hexanes+2% AcOH) to give 100 mg of the title compound as a white solid. MS: (+) m/z 350.06 (M+1).

Workup

  1. temperaturewas refluxed for 35 min under nitrogen atmosphere
  2. extractionThe aqueous layer was extracted with additional CH2Cl2
  3. dry with materialthe combined organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (0-100% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-5e9eec5ff82f456e8afe991ede9efed5
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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