Cesium carbonate → 1,1-dimethylethyl 5-cyano-2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

HRID 2401172Notes

Reaction equation

HRID 2401172 reaction equation
Br[C:2]1[C:3]([NH:10][C:11](=O)[C:12]([F:15])([F:14])[F:13])=[N:4][CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[C:17]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])[CH2:18]C(C)=O.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C.[Cu]I>[C:8]([C:6]1[CH:7]=[C:2]2[C:18]([C:17]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[C:11]([C:12]([F:15])([F:14])[F:13])[NH:10][C:3]2=[N:4][CH:5]=1)#[N:9]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 15538Tert-butyl acetoacetateHCID 145742L-ProlineHCID 86762581N-(3-bromo-5-cyano-2-pyridinyl)-2,2,2-trifluoroacetamide2×

Product 1

HCID 699286821,1-dimethylethyl 5-cyano-2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylateYield 27.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

N-(3-Bromo-5-cyano-2-pyridinyl)-2,2,2-trifluoroacetamide (Intermediate 1, 9.53 g, 32.4 mmol), tert-butyl acetoacetate (10.59 mL, 64.8 mmol), copper(I) iodide (0.617 g, 3.24 mmol), L-proline (0.746 g, 6.48 mmol) and cesium carbonate (42.2 g, 130 mmol) were added together in DMSO (65 mL) and the resulting mixture was heated at 80° C. for 18 hours. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate and washed with water and saturated ammonium chloride solution. The organic layer was separated, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-30% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a brown solid (2.77 g);

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water and saturated ammonium chloride solution
  3. customThe organic layer was separated
  4. customdried under magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography (Biotage SP4)
  7. washeluting with a gradient of 0-30% ethyl acetate and iso-hexane
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8e6efdbac3514edbaa7807c40b3d5393
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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