Dimethylformamide → 4-(2,2-Difluorovinyl)-1-[(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]pyrrolidin-2-one

HRID 1896424Notes

Reaction equation

HRID 1896424 reaction equation
Cl[CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:5][N:6]2[CH:11]=[C:10]([CH3:12])[CH:9]=[N:8][C:7]=12.[F:19][C:20]([F:28])=[CH:21][CH:22]1[CH2:26][NH:25][C:24](=[O:27])[CH2:23]1.CN(C=O)C.[H-].[Na+]>O>[F:19][C:20]([F:28])=[CH:21][CH:22]1[CH2:26][N:25]([CH2:2][C:3]2[C:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:5][N:6]3[CH:11]=[C:10]([CH3:12])[CH:9]=[N:8][C:7]=23)[C:24](=[O:27])[CH2:23]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 17948959HCID 17948959, compoundHCID 577430083-(Chloromethyl)-6-methyl-2-phenylpyrazolo[1,5-a]pyrimidine

Product 1

HCID 536291324-(2,2-Difluorovinyl)-1-[(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]pyrrolidin-2-oneYield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The above mentioned solution of intermediate x146 is added to a solution containing 4-(2,2-difluorovinyl)pyrrolidin-2-one x98 (2.64 mmol, 1.1 eq, 0.356 g), 6 ml of dry DMF and sodium hydride (60% dispersion in oil, 2.64 mmol, 1.1 eq, 0.1 g) that have been stirred at room temperature for 0.5 hour. The resulting mixture is heated up at 80° C. for 1 hour. The mixture is poured in water and extracted with AcOEt. The cumulated organic layers are washed with brine, dried over MgSO4, filtered and evaporated under reduced pressure. The residue is crystallized in AcOEt to afford 0.443 g of 4-(2,2-difluorovinyl)-1-[(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]pyrrolidin-2-one 211.

Workup

  1. additionis added to a solution
  2. temperatureThe resulting mixture is heated up at 80° C. for 1 hour
  3. extractionextracted with AcOEt
  4. washThe cumulated organic layers are washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue is crystallized in AcOEt

Sources & evidence

ORD record
ord-b57ff4dc73af4e6992559af31319064b
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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