Hydrochloric Acid → HCID 68297503, compound

HRID 919958Notes

Reaction equation

HRID 919958 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH3:16])[C:10](=[O:17])[C:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1)CCC.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:24])=[C:7]2[C:12](=[C:13]([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[N:14]=1)[N:11]([CH3:16])[C:10](=[O:17])[C:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:8]2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 34838483-(Tributylstannyl)pyridineHCID 86714158HCID 86714158, compound

Product 1

HCID 68297503HCID 68297503, compoundYield 48.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A mixture of 8-bromo-5-hydroxy-1-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (69 mg, 0.18 mmol), 3-tributylstannanyl-pyridine (0.085 mL, 0.27 mmol) and PdCl2(PPh3)2 (25 mg, 0.035 mmol) in 3 mL of DMF was heated at 120° C. for 2 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 purified sequentially by flash chromatography (15-100% EtOAc/hexanes+1% AcOH), preparative TLC (5% MeOH/CH2Cl2), and flash chromatography (0-2% MeOH/CH2Cl2) to give 34 mg of the title compound. MS: (+) m/z 388.39 (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 purified sequentially by flash chromatography (15-100% EtOAc/hexanes+1% AcOH), preparative TLC (5% MeOH/CH2Cl2), and flash chromatography (0-2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-313134175b24416d8902f7fa72eb143f
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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