Ethyl Acetate → 4-[4-ethoxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

HRID 522288Notes

Reaction equation

HRID 522288 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Cl[C:23]1[N:24]=[C:25]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH3:41])=[C:35]([C:42]([F:45])([F:44])[F:43])[CH:34]=2)[C:26]2[CH:31]=[CH:30][N:29]([CH3:32])[C:27]=2[N:28]=1.CCOC(C)=O.C[C:53]([N:55](C)C)=O>[Zn].[C-]#N.[Zn+2].[C-]#N.FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O>[CH2:40]([O:39][C:36]1[CH:37]=[CH:38][C:33]([C:25]2[C:26]3[CH:31]=[CH:30][N:29]([CH3:32])[C:27]=3[N:28]=[C:23]([C:53]#[N:55])[N:24]=2)=[CH:34][C:35]=1[C:42]([F:45])([F:44])[F:43])[CH3:41]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 31374DimethylacetamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 1178996152-chloro-4-[4-ethoxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 1178995734-[4-ethoxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2733347Palladium(II) trifluoroacetateCatalyst

Conditions

Temperature
110 °C

Procedure

Zinc (11 mg), 2-(di-tert-butylphosphino)biphenyl (23 mg), zinc cyanide (25 mg), and palladium (II) trifluoroacetate (12 mg) were added to a solution of 2-chloro-4-[4-ethoxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (125 mg) in DMAc (2.5 mL) at room temperature in an argon atmosphere, and the mixture was stirred at 110° C. for 5 hours. After the reaction mixture was cooled to room temperature, EtOAc was added thereto, followed by stirring, and the insoluble material was separated by filtration using Celite. Extraction was performed on the filtrate using EtOAc, and the extract was washed with a saturated aqueous NaHCO3 solution, water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=9:1 to 1:1), whereby 4-[4-ethoxy-3-(trifluoromethyl)phenyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (52.9 mg) was obtained as a pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringby stirring
  3. customthe insoluble material was separated by filtration
  4. extractionExtraction
  5. washthe extract was washed with a saturated aqueous NaHCO3 solution, water and saturated brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=9:1 to 1:1)

Sources & evidence

ORD record
ord-3fc5d3d9308a422daeac5b05f79cecd0
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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