Hydrochloric Acid → 7-Benzyl-4-hydroxy-8-oxo-1-pyridin-3-yl-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester

HRID 920056Notes

Reaction equation

HRID 920056 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7](I)[C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[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[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.O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 34838483-(Tributylstannyl)pyridineHCID 867141107-Benzyl-4-hydroxy-1-iodo-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester

Product 1

HCID 682972247-Benzyl-4-hydroxy-8-oxo-1-pyridin-3-yl-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl esterYield 25.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 7-benzyl-4-hydroxy-1-iodo-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (105 mg, 0.24 mmol), 3-tributylstannanyl-pyridine (133 mg, 0.36 mmol), and PdCl2(PPh3)2 (34 mg, 0.048 mmol) in 5 mL of DMF was heated at 120° C. for 2 h under N2 atmosphere. After the mixture was cooled to r.t., EtOAc and water were added. 1 M HCl was added until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH) to give 24 mg of the title compound. MS: (+) m/z 388.33 (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. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-0d560216bed3421ebf6b3b17282e9198
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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