Hydrochloric Acid → HCID 68297520, compound

HRID 920016Notes

Reaction equation

HRID 920016 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:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.Cl>C1(C)C=CC=CC=1.[Cl-].[Na+].O.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.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:31]1[CH:30]=[CH:29][CH:28]=[C:27]([O:26][CH3:25])[CH:32]=1)=[CH:8]2)=[O:4]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2734370(3-Methoxyphenyl)boronic acidHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 68297520HCID 68297520, compoundYield 79.6%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 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 (220 mg, 0.57 mmol), 3-methoxyphenylboronic acid (129 mg, 0.85 mmol), K3PO4 (240 mg, 1.13 mmol), H2O (20 mg, 1.13 mmol), SPhos (12 mg, 0.028 mmol) and Pd(OAc)2 (11 mg, 0.017 mmol) in toluene (10 mL) was heated at 100° C. under nitrogen atmosphere for 16 h. After the mixture was cooled to r.t., brine (15 mL) and EtOAc (30 mL) 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 (5-60% EtOAc/hexanes+1% AcOH) to give 189 mg of the title compound as a yellow solid. MS: (+) m/z 417.36 (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 (5-60% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-5c99572bc3724af1abd9cf768f97b13c
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

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