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

HRID 919690Notes

Reaction equation

HRID 919690 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[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]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].[C:31]([Cu])#[N:32].O.Cl>CN(C=O)C.C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([C:31]#[N:32])[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]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 867141061-Benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 682976531-Benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 79.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (200 mg, 0.43 mmol) and CuCN (77 mg, 0.86 mmol) in 5 mL of DMF was refluxed for 40 min, then cooled to r.t., and poured into a mixture of water and CH2Cl2. 4M HCl was added with vigorous stirring until no more solid was present. The aqueous layer was extracted with additional CH2Cl2 and the combined organic layer was dried over MgSO4. After evaporating the solvent in vacuo, the crude product was chromatographed (0-40% EtOAc/hexanes+2% AcOH) to give 140 mg of the title compound. MS: (+) m/z 412.12 (M+1).

Workup

  1. temperaturewas refluxed for 40 min
  2. extractionThe aqueous layer was extracted with additional CH2Cl2
  3. dry with materialthe combined organic layer was dried over MgSO4
  4. customAfter evaporating the solvent in vacuo
  5. customthe crude product was chromatographed (0-40% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-3e0c21bb02344846a1ecd742ba1cc927
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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