Sodium Iodide → 4-(1-(2,6-difluorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylbenzamide

HRID 2206186Notes

Reaction equation

HRID 2206186 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:17]2[CH:16]=[CH:15][N:14]=[C:13]([O:18]C)[C:12]=2[C:11]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([NH:26][CH3:27])=[O:25])=[CH:22][CH:21]=2)=[N:10]1.[I-].[Na+].Cl[Si](C)(C)C.C(=O)([O-])O.[Na+]>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:17]2[CH:16]=[CH:15][NH:14][C:13](=[O:18])[C:12]=2[C:11]([C:20]2[CH:21]=[CH:22][C:23]([C:24]([NH:26][CH3:27])=[O:25])=[CH:28][CH:29]=2)=[N:10]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 1179875314-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylbenzamide

Product 1

HCID 1370107694-(1-(2,6-difluorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylbenzamideYield 83.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylbenzamide (2.68 g) in acetonitrile (50 mL) were added sodium iodide (2.04 g) and chloro(trimethyl)silane (4.34 mL) was added, and the mixture was stirred at 60° C. for 3 hr. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, hexane/ethyl acetate to ethyl acetate/methanol). 1.60 g of the obtained title compound (2.15 g) was dissolved in 2-propanol (240 mL) at 80° C. To the solution was added heptane (160 mL) over 15 min, the mixture was stirred for 15 min, and allowed overnight to be cooled. The white precipitate was collected by filtration, washed with a mixed solvent of 2-propanol-heptane (3:4), and dried in vacuum to give the title compound (1.49 g).

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (basic silica gel, hexane/ethyl acetate to ethyl acetate/methanol)

Sources & evidence

ORD record
ord-e35d79560565446cb0eef163ef6113cf
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

Loading…