Triethylamine → HCID 58404692, compound

HRID 1253464Notes

Reaction equation

HRID 1253464 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:12][CH3:13])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2I)[CH:7]=1.[CH:14]1([C:17]#[CH:18])[CH2:16][CH2:15]1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]([O:12][CH3:13])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:18]#[C:17][CH:14]2[CH2:16][CH2:15]2)[CH:7]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 138823Cyclopropylacetylene3×HCID 58404704HCID 58404704, compound

Product 1

HCID 58404692HCID 58404692, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

6-bromo-3-iodo-4-methoxypyrazolo[1,5-a]pyridine (50.0 mg, 0.142 mmol), cyclopropyl acetylene (0.018 ml, 0.212 mmol), tetrakis(triphenylphosphine)palladium (0) (16.4 mg, 0.014 mmol), and copper(I) iodide (4.1 mg, 0.02 mmol) were suspended in DMF (2 ml). Triethylamine (0.039 ml, 0.283 mmol) was added, the mixture was sparged with argon for 10 minutes, then heated to 60° C. overnight. LCMS analysis indicated incomplete reaction conversion. Cyclopropyl acetylene (0.018 ml, 0.212 mmol) was added and the mixture was stirred for 6 h, at which time, LCMS analysis indicated the reaction has proceeded further, but still conversion was still incomplete. Cyclopropyl acetylene (0.036 ml, 0.426 mmol) was added and the mixture was stirred overnight. The reaction mixture was diluted in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/isohexane gradient) to afford recovered 6-bromo-3-iodo-4-methoxypyrazolo[1,5-a]pyridine (faster eluting) along with 6-bromo-3-(cyclopropylethynyl)-4-methoxypyrazolo[1,5-a]pyridine (slower eluting).

Workup

  1. customthe mixture was sparged with argon for 10 minutes
  2. stirringthe mixture was stirred overnight
  3. washwashed with saturated aqueous sodium hydrogen carbonate and brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate/isohexane gradient)
  8. customto afford
  9. customrecovered 6-bromo-3-iodo-4-methoxypyrazolo[1,5-a]pyridine (
  10. washfaster eluting) along with 6-bromo-3-(cyclopropylethynyl)-4-methoxypyrazolo[1,5-a]pyridine (
  11. washslower eluting)

Sources & evidence

ORD record
ord-c750cc0483ac477fbafe213250d45e7b
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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