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 2422977Notes

Reaction equation

HRID 2422977 reaction equation
[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

Participants

7

Reactant 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

Product 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-oneYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-2ba148b953044688972137933f4aea51
Source dataset
uspto-grants-2011_06
Patent number
US07960411B2

Reaction notes

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