Triethylamine → 4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-[(trimethylsilyl)ethynyl]pyrazolo[1,5-a]pyridine

HRID 1253468Notes

Reaction equation

HRID 1253468 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[CH:8]=[C:7]([O:17][CH3:18])[C:6]=12.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21].C(N(CC)CC)C.[Al]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.CN(C=O)C>[CH3:18][O:17][C:7]1[C:6]2[N:5]([N:4]=[CH:3][C:2]=2[C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19])[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[CH:8]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 5359268AluminumHCID 448167683-iodo-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

Product 1

HCID 584048004-methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-[(trimethylsilyl)ethynyl]pyrazolo[1,5-a]pyridine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

3-iodo-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (860. mg, 2.43 mmol), tetrakis(triphenylphosphine)palladium(0) (281 mg, 0.243 mmol), trimethylsilylacetylene (1.01 ml, 7.29 mmol) and copper (I) iodide (277 mg, 1.46 mmol) were combined in a round bottom flask. DMF (25 mL) and triethylamine (0.677 mL, 4.86 mmol) were added, then the flask was wrapped with aluminum foil and sparged with nitrogen for 5 minutes. The reaction was stirred at ambient temperature for 30 mins, then diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was separated and the aqueous layer was back extracted two times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The liquid was purified by column chromatography on silica gel (methanol/ethyl acetate gradient) to give 4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-[(trimethylsilyl)ethynyl]pyrazolo[1,5-a]pyridine LRMS (ESI) calculated for C17H21N4OSi [M+H]+, 325.1; found 325.1.

Workup

  1. customsparged with nitrogen for 5 minutes
  2. additiondiluted with ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was back extracted two times with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe liquid was purified by column chromatography on silica gel (methanol/ethyl acetate gradient)

Sources & evidence

ORD record
ord-bd1634edf80b41d4b594d028c2f72a12
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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