Ethyl Acetate → 5-Hydroxy-2-oxo-1,3-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 919873Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:23])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10](=[O:21])[C:9](Br)=[CH:8]2)=[O:4].[C:24]1([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCOC(C)=O>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:23])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10](=[O:21])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-bromo-5-hydroxy-2-oxo-1-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (300 mg, 0.8 mmol), PhSnBu3 (0.31 mL, 0.96 mmol), and PdCl2(PPh3)2 (112 mg, 0.16 mmol) in DMF (8 mL) was heated at 120° C. under nitrogen atmosphere for 2 h. After the mixture was cooled to r.t., brine (10 mL) and EtOAc (50 mL) were added. The aqueous layer was extracted with additional EtOAc and the organic layers were combined, washed with water, and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was chromatographed (0-50% EtOAc/hexanes+2% AcOH) to give 195 mg of the title compound as a light yellow solid. MS: (−) m/z 371.32 (M−1).

Workup

temperatureAfter the mixture was cooled to r.t.
extractionThe aqueous layer was extracted with additional EtOAc
washwashed with water
dry with materialdried over MgSO4
customAfter evaporating the solvent in vacuo
customthe crude product was chromatographed (0-50% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record: ord-1f48e82e4f3d4b18b55dfa6b74a870b5
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09271970B2

Reaction notes

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