Potassium Carbonate → 4-{4-[2-(1-cyclopropylpiperidin-4-yl)ethoxy]-3-(trifluoromethyl)phenyl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

HRID 522298Notes

Reaction equation

HRID 522298 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:18]=[CH:17][N:16]([CH3:19])[C:10]=3[N:11]=[C:12]([C:14]#[N:15])[N:13]=2)=[CH:4][C:3]=1[C:20]([F:23])([F:22])[F:21].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:41][CH2:42][CH:43]2[CH2:48][CH2:47][N:46]([CH:49]3[CH2:51][CH2:50]3)[CH2:45][CH2:44]2)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CC(N(C)C)=O.O.CCOC(C)=O>[CH:49]1([N:46]2[CH2:47][CH2:48][CH:43]([CH2:42][CH2:41][O:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]4[C:9]5[CH:18]=[CH:17][N:16]([CH3:19])[C:10]=5[N:11]=[C:12]([C:14]#[N:15])[N:13]=4)=[CH:4][C:3]=3[C:20]([F:23])([F:22])[F:21])[CH2:44][CH2:45]2)[CH2:50][CH2:51]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 1178996782-(1-Cyclopropylpiperidin-4-yl)ethyl 4-methylbenzenesulfonateHCID 1370152264-[4-hydroxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

Product 1

HCID 1178995874-{4-[2-(1-cyclopropylpiperidin-4-yl)ethoxy]-3-(trifluoromethyl)phenyl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrileYield 36.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

4-[4-Hydroxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (100 mg) and potassium carbonate (87 mg) were added to a solution of 2-(1-cyclopropylpiperidin-4-yl)ethyl 4-methylbenzenesulfonate (152 mg) in DMAc (2 mL) at room temperature, and the mixture was stirred at 80° C. for 1 hour. After the reaction mixture was cooled to room temperature, EtOAc, water, and a saturated aqueous NaHCO3 solution were added thereto, and the mixture was stirred. Extraction was performed on the mixture using EtOAc, and the extract was washed with water and 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), whereby 4-{4-[2-(1-cyclopropylpiperidin-4-yl)ethoxy]-3-(trifluoromethyl)phenyl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (54 mg) was obtained as pale yellow powder.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred
  3. extractionExtraction
  4. washthe extract was washed with water and saturated brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (Hex:CHCl3=50:50 to 0:100)

Sources & evidence

ORD record
ord-266f9d362c7e4404ae07af79f5e9eeaf
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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