Hydrochloric Acid → HCID 68297680, compound

HRID 919886Notes

Reaction equation

HRID 919886 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].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.Cl>C1(C)C=CC=CC=1.[Cl-].[Na+].O.CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O>[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]1[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=1)=[CH:8]2)=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297680HCID 68297680, compoundYield 20.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (60 mg, 0.15 mmol), 4-methoxyphenylboronic acid (35 mg, 0.23 mmol), K3PO4 (65 mg, 0.31 mmol), SPhos (3.2 mg, 0.0077 mmol) and Pd(OAc)2 (3.1 mg, 0.0046 mmol) in toluene (3 mL) was heated at 100° C. under nitrogen atmosphere for 16 h. After the mixture was cooled to r.t., brine and EtOAc were added. 1 M HCl was added with stirring until pH was about 3, and the aqueous layer extracted with additional EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (0-60% EtOAc/hexanes+2% AcOH) to give 13 mg of the title compound. MS: (+) m/z 417.30 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionthe aqueous layer extracted with additional EtOAc
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (0-60% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-ba95a064c33a4386812c47d56b7fe1d7
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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