Sodium Carbonate → N-[5-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-propionamide

HRID 1774848Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1774848
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:24]1[CH:25]=[C:26]([CH2:30][NH:31][C:32](=[O:35])[CH2:33][CH3:34])[CH:27]=[N:28][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1[C:24]1[CH:25]=[C:26]([CH2:30][NH:31][C:32](=[O:35])[CH2:33][CH3:34])[CH:27]=[N:28][CH:29]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 86679131HCID 86679131, VerbindungHCID 86679194N-(5-Bromo-pyridin-3-ylmethyl)-propionamide

Produkt 1

HCID 86679195N-[5-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-propionamideAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a mixture of 7-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-22, 168 g, 0.55 mmol) and N-(5-bromo-pyridin-3-ylmethyl)-propionamide (122 mg, 0.5 mmol) in DMF (3 mL), purged with argon for 1 min, was added bis(triphenylphosphine)palladium (II)chloride (38 mg, 0.054 mmol) and 1 N aq. Na2CO3 (2.5 mL). Then, the resulting reaction mixture was heated in a microwave at 110° C. for 45 min. After cooling to room temperature, it was diluted with EtOAc (5 mL) and poured into a satd. aq. solution of NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (3×5 mL) and combined organics were washed with water and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was then purified by prep-HPLC to afford the title compound (30 mg, 18%) as a white solid. MS: 342.1 (M+H+)+.

Aufarbeitung

  1. custompurged with argon for 1 min
  2. customThen, the resulting reaction mixture
  3. temperatureAfter cooling to room temperature
  4. additionpoured into a satd
  5. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  6. washcombined organics were washed with water and brine (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-dd7dfea26d814da889e94f2031a8a8b2
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260408B2

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