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

HRID 919829Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:14]([OH:15])=[C:13]2[C:8]([CH:9]=[CH:10][C:11](=[O:23])[N:12]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:7](I)[N:6]=1)=[O:4].[CH3:25][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:14]([OH:15])=[C:13]2[C:8]([CH:9]=[CH:10][C:11](=[O:23])[N:12]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:7]([CH3:25])[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 1-benzyl-8-hydroxy-5-iodo-2-oxo-1,2-dihydro-[1,6]naphthyridine-7-carboxylic acid methyl ester (86 mg, 0.197 mmol), tetramethyltin (0.14 mL, 0.99 mmol) and PdCl2(PPh3)2 (28 mg, 0.039 mmol) in DMF (4 mL) was heated at 120° C. for 2 h under N2 atmosphere. After cooling to r.t., EtOAc (50 mL) and brine (10 mL) were added. 1 M HCl was added until pH about 2-3. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4, and concentrated. The crude product was purified by silica gel chromatography (0-3% MeOH/CH2Cl2) to give 18 mg of the title compound as a white solid. MS: (+) m/z 325.28 (M+1).

Workup

temperatureAfter cooling to r.t.
extractionThe aqueous layer was extracted with additional EtOAc
dry with materialdried over MgSO4
concentrationconcentrated
customThe crude product was purified by silica gel chromatography (0-3% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-8de94e140e664c3a966b2611627b8f21
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09271970B2

Reaction notes

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