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Hydrochloric Acid → 1-Benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1411070
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1411070
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:40]1[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=1)CCC.CCOC(C)=O.Cl>CN(C=O)C.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.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:34])=[C:7]2[C:12](=[C:13]([C:40]3[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=3)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1)=[CH:8]2)=[O:4]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 34838483-(Tributylstannyl)pyridineHCID 867141831-Benzyl-8-bromo-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Produkt 1

HCID 682974461-Benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester
Ausbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 1-benzyl-8-bromo-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (76 mg, 0.14 mmol), 3-tributylstannanyl-pyridine (0.070 mL, 0.21 mmol) and PdCl2(PPh3)2 (20 mg, 0.029 mmol) in 4 mL of DMF was heated at 120° C. for 2 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and water were added. 1 M HCl was added until pH was about 3. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and brine, and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was purified by silica gel chromatography (5-95% EtOAc/hexanes+1% AcOH) to give 29 mg of the title compound. MS: (+) m/z 532.30 (M+1).

Aufarbeitung

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washthe combined organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent in vacuo
  6. customthe crude product was purified by silica gel chromatography (5-95% EtOAc/hexanes+1% AcOH)

Quellen und Nachweise

ORD-Eintrag
ord-db100358a54140459f5fe3605baeba88
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08921389B2

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