Cesium carbonate → HCID 66730799, compound

HRID 1027997Notes

Reaction equation

HRID 1027997 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][CH:6]=[C:5]2[C:12]#[N:13].[CH:14]1(Br)[CH2:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH:14]1([N:7]2[C:8]3[C:4](=[CH:3][C:2]([F:1])=[C:10]([CH3:11])[CH:9]=3)[C:5]([C:12]#[N:13])=[CH:6]2)[CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 78110BromocyclobutaneHCID 53402097HCID 53402097, compound

Product 1

HCID 66730799HCID 66730799, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-fluoro-6-methyl-1H-indole-3-carbonitrile (1.0 g, 5.8 mmol), cyclobutylbromide (0.81 mL, 8.6 mmol) and cesium carbonate (3.9 g, 12.1 mmol) in DMF (10 mL) was stirred at 90° C. overnight. The mixture was then poured into ice water and extracted with ethyl acetate. The organics were combined and washed with water, brine and dried over Na2SO4 and evaporated. The residue was purified by flash chromatography with 5-35% ethyl acetate in hexane to give 1-cyclobutyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (1.2 g, 92%). 1H NMR (500 MHz, CDCl3): 7.68 (1H, s), 7.35 (1H, d, J=9.6 Hz), 7.17 (1H, d, J=6.1 Hz), 4.83-4.79 (1H, m), 2.68-2.60 (2H, m), 2.48-2.37 (5H, m), 2.05-1.96 (2H, m).

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe residue was purified by flash chromatography with 5-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b37c5968f7bb4b918729a308230c9c1a
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

Loading…