1,10-Phenanthroline → 1-(3-Chloro-phenyl)-3-methanesulfonyl-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

HRID 1261605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1261605
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[C:13](=[O:24])[N:14]([C:17]4[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=4)[CH2:15][CH2:16][C:11]=3[C:10]([S:25]([CH3:28])(=[O:27])=[O:26])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[C:29]1(=[O:35])[NH:34][CH2:33][CH2:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.[OH-].[NH4+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[C:13](=[O:24])[N:14]([C:17]4[CH:22]=[CH:21][C:20]([N:34]5[CH2:33][CH2:32][CH2:31][CH2:30][C:29]5=[O:35])=[CH:19][CH:18]=4)[CH2:15][CH2:16][C:11]=3[C:10]([S:25]([CH3:28])(=[O:27])=[O:26])=[N:9]2)[CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 5

HCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 126652-PiperidoneHCID 14923Ammonium HydroxideHCID 222404561-(3-Chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Produkt 1

HCID 102287011-(3-Chloro-phenyl)-3-methanesulfonyl-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-oneAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Part B. In a round bottomed flask were combined 1-(3-chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (1.00 g, 1.89 mmol), δ-valerolactam (0.36 g, 3.79 mmol), anhydrous powdered potassium carbonate (1.05 g, 7.58 mmol), cuprous iodide (0.072 g, 0.38 mmol), and 1,10-phenanthroline (0.068 g, 0.38 mmol). The flask was purged with argon and degassed methylsulfoxide (10 mL) was added before heating to 120° C. Upon completion of the reaction, as judged by TLC or LC/MS, the reaction was cooled to ambient temperature and 50 mL each of 3M ammonium hydroxide and dichloromethane were added. The phases were separated and the aqueous extracted with an additional 30 mL of dichloromethane. The combined dichloromethane extracts are washed successively four times with water and once with brine. The solution was dried over sodium sulfate, filtered, and evaporated to give an oil that was purified by flash column chromatography eluting with ethylacetate to give 0.424 g (45%) of 1-(3-chloro-phenyl)-3-methanesulfonyl-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one as a colorless solid. The material may be recrystallized from acetonitrile. 1H NMR (DMSO-d6) δ 7.79 (t, 1H, J=2 Hz), 7.63-7.49 (m, 3H), 7.32 (ab q, 4H, J=21.9 Hz), 4.10 (t, 2H, J=6 Hz), 3.58 (t, 2H, J=5 Hz), 3.36 (s, 3H), 3.19 (t, 2H, J=6 Hz), 2.37 (t, 2H, J=5 Hz), 1.83 (m, 4H). LC/MS (ES+): 498.9/500.9 (Cl pattern) (>95% pure by ELSD).

Aufarbeitung

  1. customIn a round bottomed flask were combined
  2. customThe flask was purged with argon
  3. customdegassed methylsulfoxide (10 mL)
  4. additionwas added
  5. customUpon completion of the reaction
  6. temperaturethe reaction was cooled to ambient temperature
  7. customThe phases were separated
  8. extractionthe aqueous extracted with an additional 30 mL of dichloromethane
  9. washThe combined dichloromethane extracts are washed successively four times with water
  10. dry with materialThe solution was dried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customto give an oil that
  14. customwas purified by flash column chromatography
  15. washeluting with ethylacetate

Quellen und Nachweise

ORD-Eintrag
ord-680705bcafb84c20a72d0ed1bc537b6f
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470854B2

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