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Hydrochloric Acid → 5-Hydroxy-2-oxo-1,3-diphenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 919955
Notes
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Reaction equation

HRID 919955 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1)CCC.CN(C=O)C.Cl>[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.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[C:13]([C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)[N:14]=1)[N:11]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 34838483-(Tributylstannyl)pyridineHCID 867141578-Bromo-5-hydroxy-2-oxo-1,3-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682974225-Hydroxy-2-oxo-1,3-diphenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester
Yield 58.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 8-bromo-5-hydroxy-2-oxo-1,3-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.13 mmol), 3-tributylstannanyl-pyridine (0.064 mL, 0.20 mmol) and PdCl2(PPh3)2 (19 mg, 0.027 mmol) in 3 mL, of DMF was heated at 120° C. for 2 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and brine were added. 1 M HCl was added with stirring until pH was about 3-4. 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 crude product was chromatographed (15-100% EtOAc/hexanes+1% AcOH) to give 34 mg of the title compound as a pale yellow solid. MS: (+) m/z 450.30 (M+1).

Workup

  1. extractionThe aqueous layer was extracted with additional EtOAc
  2. washthe combined organic layer was washed with water
  3. dry with materialdried over MgSO4
  4. customAfter evaporating the solvent in vacuo
  5. customthe crude product was chromatographed (15-100% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-90c70e766ea1468e9f0ff7c2d810d524
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09271970B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes