Potassium Iodide → 2-[4-(2-{4-[2-cyano-7-(tetrahydrofuran-2-yl methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidin-1-yl]-N,N-dimethylacetamide monohydrochloride

HRID 522300Notes

Reaction equation

HRID 522300 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[Cl:9][CH2:10][C:11]([N:13]([CH3:15])[CH3:14])=[O:12].Cl.[NH:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[C:33]4[CH:42]=[CH:41][N:40]([CH2:43][CH:44]5[CH2:48][CH2:47][CH2:46][O:45]5)[C:34]=4[N:35]=[C:36]([C:38]#[N:39])[N:37]=3)=[CH:28][C:27]=2[C:49]([F:52])([F:51])[F:50])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>CCOC(C)=O.O.C(#N)C>[ClH:9].[C:38]([C:36]1[N:37]=[C:32]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:24][CH2:23][CH:20]3[CH2:21][CH2:22][N:17]([CH2:10][C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH2:18][CH2:19]3)=[C:27]([C:49]([F:50])([F:51])[F:52])[CH:28]=2)[C:33]2[CH:42]=[CH:41][N:40]([CH2:43][CH:44]3[CH2:48][CH2:47][CH2:46][O:45]3)[C:34]=2[N:35]=1)#[N:39]

Participants

9

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 516892Sodium BicarbonateHCID 1178996134-{4-[2-(piperidin-4-yl)ethoxy]-3-(trifluoromethyl)phenyl}-7-(tetrahydrofuran-2-yl methyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile monohydrochloride

Product 1

HCID 1178996402-[4-(2-{4-[2-cyano-7-(tetrahydrofuran-2-yl methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidin-1-yl]-N,N-dimethylacetamide monohydrochloride

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Potassium carbonate (62 mg), potassium iodide (25 mg), and 2-chloro-N,N-dimethylacetamide (18 μL) were added to a mixture of 4-{4-[2-(piperidin-4-yl)ethoxy]-3-(trifluoromethyl)phenyl}-7-(tetrahydrofuran-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile monohydrochloride (80 mg) and acetonitrile (3.2 mL) at room temperature, and the mixture was stirred at 60° C. for 2 hours. After the reaction mixture was cooled to room temperature, the reaction mixture was diluted with EtOAc. Then, a saturated aqueous NaHCO3 solution and water were added thereto, then extraction thereof was performed using EtOAc, and the extract was washed with saturated brine. The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (Hex:CHCl3=50:50 to 0:100). The obtained product was dissolved in EtOAc (1 mL), then a 4 M solution of hydrogen chloride in EtOAc (37 μL) was added thereto at room temperature, and the mixture was stirred at the same temperature for 1 hour. The precipitate was collected by filtration, whereby 2-[4-(2-{4-[2-cyano-7-(tetrahydrofuran-2-yl methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(trifluoromethyl)phenoxy}ethyl)piperidin-1-yl]-N,N-dimethylacetamide monohydrochloride (57 mg) was obtained as a pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. extractionextraction
  3. washthe extract was washed with saturated brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by basic silica gel column chromatography (Hex:CHCl3=50:50 to 0:100)
  8. dissolutionThe obtained product was dissolved in EtOAc (1 mL)
  9. additiona 4 M solution of hydrogen chloride in EtOAc (37 μL) was added
  10. stirringat room temperature, and the mixture was stirred at the same temperature for 1 hour
  11. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-53fabdb22b184135ad9f39f7489b25e8
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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