Sodium hydride → 1-[(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one

HRID 2043656Notes

Reaction equation

HRID 2043656 reaction equation
[F:1][C:2]([F:10])=[CH:3][CH:4]1[CH2:8][NH:7][C:6](=[O:9])[CH2:5]1.[H-].[Na+].[Br:13][C:14]1[CH:15]=[C:16]2[C:22]([CH2:23]Br)=[N:21][N:20](C(OC(C)(C)C)=O)[C:17]2=[N:18][CH:19]=1>CN(C=O)C.O>[Br:13][C:14]1[CH:15]=[C:16]2[C:22]([CH2:23][N:7]3[CH2:8][CH:4]([CH:3]=[C:2]([F:10])[F:1])[CH2:5][C:6]3=[O:9])=[N:21][NH:20][C:17]2=[N:18][CH:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 17948959HCID 17948959, compoundHCID 67085957tert-Butyl 5-bromo-3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

Product 1

HCID 1785160371-[(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-oneYield 4.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-(2,2-difluorovinyl)pyrrolidin-2-one x98 (2.86 mmol, 2 eq, 0.42 g) in dry DMF (5 ml) maintained at 0° C. is added natrium hydride (60% dispersion in oil; 2.86 mmol, 2 eq, 0.114 g). The resulting mixture is stirred at room temperature for 0.5 hour and tert-butyl 5-bromo-3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate x155 (1.43 mmol, 1 eq, 0.56 g) dissolved in DMF (2 ml) is added. The resulting mixture is stirred overnight at room temperature. The mixture is poured in water and extracted with AcOEt. The cumulated organic layers are dried over MgSO4, filtered and evaporated under reduced pressure. The crude mixture is purified twice by chromatography on silicagel (CH2Cl2/MeOH/NH4OH 98/2/0.2) to afford pure 1-[(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one 221 (0.025 g).

Workup

  1. additionis added
  2. stirringThe resulting mixture is stirred overnight at room temperature
  3. extractionextracted with AcOEt
  4. dry with materialThe cumulated organic layers are dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude mixture is purified twice by chromatography on silicagel (CH2Cl2/MeOH/NH4OH 98/2/0.2)

Sources & evidence

ORD record
ord-3961dd6e7c6443d3be06d75334add006
Source dataset
uspto-grants-2013_11
Patent number
US08586623B2

Reaction notes

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