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 919924Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 919924
[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]

Komponenten

11

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5fc9c1deda84439e8f85104c238737c8
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09271970B2

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