Hydrochloric Acid → 1-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1410927Notes

Reaction equation

HRID 1410927 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][N:26]([CH3:36])[C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][N:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.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:29]=[N:28][C:27]([N:26]([CH3:36])[CH3:25])=[N:32][CH:31]=1)=[CH:8]2)=[O:4]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 45088929[2-(Dimethylamino)pyrimidin-5-yl]boronic acidHCID 682974771-Benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682974441-Benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 32%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
105 °C

Procedure

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (80 mg, 0.21 mmol), 2-dimethylaminopyrimidine-5-boronic acid (52 mg, 0.31 mmol), K3PO4 (87 mg, 0.41 mmol), H2O (7.4 mg, 0.41 mmol), SPhos (4.2 mg, 0.010 mmol) and Pd(OAc)2 (4.2 mg, 0.0062 mmol) in toluene (5 mL) was heated at 105° C. under nitrogen atmosphere for 16 h. After the mixture was cooled to r.t., brine (10 mL) and EtOAc (20 mL) were added. 1 M HCl was added with stirring until pH was about 3-4, and the organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (10-100% EtOAc/hexanes+2% AcOH) to give 29 mg of the title compound as a bright yellow solid. MS: (+) m/z 432.29 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. dry with materialthe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified by silica gel chromatography (10-100% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-f24f0031fab045d7b3cf6a765e111d9a
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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