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

HRID 1410685Notes

Reaction equation

HRID 1410685 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9](Br)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:30]#[C:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)CCC.Cl>CN(C=O)C.[Cl-].[Na+].O.CCOC(C)=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](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:30]#[C:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[CH:8]2)=[O:4]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 630640Tributyl(2-phenylethynyl)stannaneHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682975811-Benzyl-5-hydroxy-2-oxo-3-phenylethynyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 85%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (500 mg, 1.29 mmol), tributyl-phenylethynyl-stannane (0.54 mL, 1.54 mmol), and PdCl2(PPh3)2 (180 mg, 0.26 mmol) in 10 mL of DMF was heated at 120° C. for 2 h under N2 atmosphere. The mixture was cooled to r.t. and diluted with brine (10 mL) and EtOAc (40 mL). 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 the solvent was evaporated in vacuo, the crude residue was chromatographed (0-60% EtOAc/hexanes+2% AcOH) to give 450 mg of the title compound as a yellow solid. MS: (+) m/z 411.11 (M+1).

Workup

  1. temperatureThe 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 the solvent was evaporated in vacuo
  6. customthe crude residue was chromatographed (0-60% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-67b6756b88e04e2182fb618ec0f83166
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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