Diisopropylamine → 5-Methyl-3-((4-((trimethylsilyl)ethynyl)-1H-pyrazol-1-yl)methyl)isoxazole

HRID 2205870Notes

Reaction equation

I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]2[CH:12]=[C:11]([CH3:13])[O:10][N:9]=2)[CH:6]=1.[CH3:14][Si:15]([C:18]#[CH:19])([CH3:17])[CH3:16].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>[CH3:13][C:11]1[O:10][N:9]=[C:8]([CH2:7][N:5]2[CH:6]=[C:2]([C:19]#[C:18][Si:15]([CH3:17])([CH3:16])[CH3:14])[CH:3]=[N:4]2)[CH:12]=1

Participants

Conditions

Temperature: 60 °C

Procedure

3-((4-Iodo-1H-pyrazol-1-yl)methyl)-5-methylisoxazole (30) (0.7 g, 2.42 mmol) and trimethylsilylacetylene (0.326 g, 3.32 mmol) were dissolved in DMF (5 ml) and placed under argon. Diisopropylamine (0.47 ml, 3.3 mmol), copper(I) 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 at 60° C. for 1 hour. It was cooled to room temperature and diluted with water (20 ml) and ethyl acetate (30 ml). The organic layer was collected, dried and concentrated. The crude product was purified by flash silica chromatography eluting with 5% ethyl acetate in DCM. The pure fractions provided the title compound as a brown oil which solidified on standing (550 mg, 88%). 1H-NMR (500 MHz, CDCl3): 0.21 (s, 9H), 2.38 (s, 3H), 5.29 (s, 2H), 5.88 (s, 1H), 7.58 (s, 1H), 7.61 (s, 1H).

Workup

customthe flask was flushed with argon
temperatureIt was cooled to room temperature
additiondiluted with water (20 ml) and ethyl acetate (30 ml)
customThe organic layer was collected
customdried
concentrationconcentrated
customThe crude product was purified by flash silica chromatography
washeluting with 5% ethyl acetate in DCM

Sources & evidence

ORD record: ord-5bcb90f1fc4b46eeaec2febb5027c25d
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371319B2

Reaction notes

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