Diisopropylamine → N,N-Dimethyl-2-(4-((trimethylsilyl)ethynyl)-1H-pyrazol-1-yl)acetamide

HRID 2205910Notes

Reaction equation

HRID 2205910 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]([N:10]([CH3:12])[CH3:11])=[O:9])[CH:6]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(NC(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:11][N:10]([CH3:12])[C:8](=[O:9])[CH2:7][N:5]1[CH:6]=[C:2]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[CH:3]=[N:4]1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 644307842-(4-Iodo-1H-pyrazol-1-yl)-N,N-dimethylacetamide

Product 1

HCID 68290932N,N-Dimethyl-2-(4-((trimethylsilyl)ethynyl)-1H-pyrazol-1-yl)acetamideYield 91.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Iodo-1H-pyrazol-1-yl)-N,N-dimethylacetamide (Preparation 99, 0.68 g, 2.42 mmol) and trimethylsilylacetylene (0.326 g, 3.32 mmol) were dissolved in dry DMF (5 ml) and placed under argon. Diisopropylamine (0.47 ml, 3.3 mmol), copper (1) iodide (30 mg, 0.16 mmol), triphenylphosphine (126 mg, 0.242 mmol) and palladium acetate (40 mg, 0.16 mmol) were added and the flask was flushed with argon. The reaction was heated to 60° C. for 1 hour. The reaction was cooled to room temperature and diluted with ethyl acetate (30 ml). The organic solution was washed with water, brine, dried over sodium sulphate and filtered. The solvent was removed in vacuum and the crude purified on silica gel column chromatography eluting with neat ethyl acetate to afford the title compound as a pale yellow powder (0.55 g, 91%). 1H-NMR (500 MHz, CDCl3): δ 0.21 (s, 9H), 2.96 (s, 3H), 3.04 (s, 3H), 4.92 (s, 2H), 7.59 (s, 1H), 7.65 (s, 1H).

Workup

  1. customthe flask was flushed with argon
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate (30 ml)
  4. washThe organic solution was washed with water, brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customThe solvent was removed in vacuum
  8. customthe crude purified on silica gel column chromatography
  9. washeluting with neat ethyl acetate

Sources & evidence

ORD record
ord-c722d32839834f05a776eb7ceeaadf44
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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