Potassium Carbonate → HCID 67201862, compound

HRID 1888531Notes

Reaction equation

HRID 1888531 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C12BC(CCC1)CCC2.[C:24]1([S:30]([N:33]2[C:37]3[CH:38]=[N:39][C:40]([C:43]#[N:44])=[C:41](Br)[C:36]=3[C:35]3[CH:45]=[CH:46][CH:47]=[N:48][C:34]2=3)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>O.CN(C=O)C.ClCCl.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:41]2[C:36]3[C:35]4[CH:45]=[CH:46][CH:47]=[N:48][C:34]=4[N:33]([S:30]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)(=[O:32])=[O:31])[C:37]=3[CH:38]=[N:39][C:40]=2[C:43]#[N:44])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-MethylenepiperidineHCID 58266792HCID 58266792, compound

Product 1

HCID 67201862HCID 67201862, compoundYield 38%

Reagents, catalysts & solvents 4

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-methylene-piperidine-1-carboxylic acid tert-butyl ester (0.70 g, 3.55 mmol) and 9-borabicyclo[3,3,1]nonane (0.5M solution in THF, 7 mL, 3.5 mmol) were heated at reflux for 1.5 h. The reaction mixture was cooled and added to a degassed mixture of 9-benzenesulfonyl-5-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (0.41 g, 1.0 mmol), [1,1-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (0.090 g, 0.11 mmol) and potassium carbonate (0.18 g, 1.3 mmol) in water (1 mL) and DMF (10 mL) and the reaction mixture was then heated at 65° C. for 1.25 h. After cooling to ambient temperature the reaction mixture was then diluted with water (5 mL) and dichloromethane (10 mL). The aqueous phase was extracted with dichloromethane (2×15 mL) and the combined organic phase was washed with brine (15 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated with pentane (10 mL) and the resultant material was purified by flash chromatography (silica, 5 g column, SPE-Si II, 0-2% methanol in DCM) to afford title compound as a yellow solid (202 mg, 38%). 1H NMR (CDCl3, 400 MHz): 9.81 (s, 1H), 8.79 (dd, J=4.8, 1.6 Hz, 1H), 8.33-8.27 (m, 3H), 7.66-7.60 (m, 1H), 7.55-7.46 (m, 3H), 4.22-4.01 (m, 2H), 3.34-3.27 (m, 2H), 2.62-2.50 (m, 2H), 1.97-1.76 (m, 2H), 1.72-1.46 (m, 3H), 1.45 (s, 9H).

Workup

  1. temperaturewere heated
  2. temperatureat reflux for 1.5 h
  3. temperatureThe reaction mixture was cooled
  4. temperatureAfter cooling to ambient temperature the reaction mixture
  5. extractionThe aqueous phase was extracted with dichloromethane (2×15 mL)
  6. washthe combined organic phase was washed with brine (15 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was triturated with pentane (10 mL)
  11. customthe resultant material was purified by flash chromatography (silica, 5 g column, SPE-Si II, 0-2% methanol in DCM)

Sources & evidence

ORD record
ord-80509290003d407cb9728c709aef8aa6
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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