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

HRID 1410977Notes

Reaction equation

HRID 1410977 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].[CH3:31][O:32][C:33]1[CH:34]=[N:35][CH:36]=[C:37]([Sn](CCCC)(CCCC)CCCC)[CH:38]=1.CCOC(C)=O.Cl>CN(C=O)C.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([C:37]3[CH:36]=[N:35][CH:34]=[C:33]([O:32][CH3:31])[CH:38]=3)[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

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 441182315-Methoxy-3-(tributylstannyl)pyridineHCID 867141061-Benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682976601-Benzyl-5-hydroxy-8-(5-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 60.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

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 (70 mg, 0.15 mmol), 3-methoxy-5-tributylstannanyl-pyridine (90 mg, 0.23 mmol) and PdCl2(PPh3)2 (21 mg, 0.030 mmol) in 3 mL of DMF was heated at 120° C. for 3 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and brine were added. 1 M HCl was added with stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was chromatographed (10-85% EtOAc/hexanes+1% AcOH) to give 45 mg of the title compound as a light yellow solid. MS: (+) m/z 494.51 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washthe combined organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent in vacuo
  6. customthe crude product was chromatographed (10-85% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-e3646749d03c4326b06c85d46312e88c
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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