Piperidine → 6-ethynyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide

HRID 2363719Notes

Reaction equation

HRID 2363719 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[N:11]=[C:12]3[CH:17]=[CH:16][C:15]([C:18]#N)=[CH:14][N:13]3[CH:20]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:21][Si](C#C)(C)C.N1CCCCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+]>[C:18]([C:15]1[CH:16]=[CH:17][C:12]2[N:13]([CH:20]=[C:10]([C:8]([NH:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[O:9])[N:11]=2)[CH:14]=1)#[CH:21]

Participants

6

Reactant 3

HCID 8082PiperidineHCID 66111TrimethylsilylacetyleneHCID 44135940N-phenyl-6-cyanoimidazo[1,2-a]pyridine-2-carboxamide2×

Product 1

HCID 247716676-ethynyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
25 °C

Procedure

0.2 g of 6-iodo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide (Intermediate 2), 156 μL of trimethylsilylacetylene, 20 mg of dichlorobis(triphenylphosphine)palladium and 2 mL of piperidine are placed in a 20 mL microwave tube. The mixture is heated for 15 minutes in a microwave machine set at 130° C. After cooling, the mixture is poured into 50 mL of saturated aqueous ammonium chloride solution. The resulting mixture is extracted twice with 70 mL of ethyl ether. The combined organic phases are separated out by settling, dried and concentrated to dryness under reduced pressure. The residue is taken up in 4 mL of a 1M solution of tetrabutylammonium fluoride in THF and stirred for 16 hours at 25° C. After evaporating the reaction medium to dryness, the residue is chromatographed on silica, eluting with a mixture of cyclohexane and ethyl acetate (gradient from 0 to 35%) to give 30 mg of 6-ethynyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a beige-coloured solid.

Workup

  1. temperatureThe mixture is heated for 15 minutes in a microwave machine
  2. customset at 130° C
  3. temperatureAfter cooling
  4. extractionThe resulting mixture is extracted twice with 70 mL of ethyl ether
  5. customThe combined organic phases are separated out
  6. customdried
  7. concentrationconcentrated to dryness under reduced pressure
  8. customAfter evaporating the reaction medium to dryness
  9. customthe residue is chromatographed on silica
  10. washeluting with a mixture of cyclohexane and ethyl acetate (gradient from 0 to 35%)

Sources & evidence

ORD record
ord-2546e72ed24140998518284aa0b78bcb
Source dataset
uspto-grants-2014_04
Patent number
US08691990B2

Reaction notes

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