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

HRID 1410669Notes

Reaction equation

HRID 1410669 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].[CH3:26][Sn](C)(C)C.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:25])=[C:7]2[C:12](=[C:13]([CH3:26])[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

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 11661TetramethyltinHCID 867141041-Benzyl-8-bromo-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682972371-Benzyl-5-hydroxy-3,8-dimethyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 107.1%

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-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (162 mg, 0.40 mmol), tetramethyltin (0.3 mL, 2.0 mmol) and PdCl2(PPh3)2 (56 mg, 0.08 mmol) in 5 mL of DMF was heated at 120° C. under nitrogen atmosphere for 1 h. After the mixture was cooled to r.t., brine (10 mL) and EtOAc (40 mL) was added. 1M HCl was added until pH was about 3. 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 residue was chromatographed (0-50% EtOAc/hexanes+2% AcOH) to give 145 mg of the title compound as a white solid. MS: (+) m/z 339.11 (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 residue was chromatographed (0-50% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-e027c50abf0d4634aec5c33ca28847d5
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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