Trimethylsilylacetylene → 1-(Tetrahydro-2H-pyran-2-yl)-5-((trimethylsilyl)ethynyl)-1H-indazole

HRID 1057099Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.[CH3:17][Si:18]([C:21]#[CH:22])([CH3:20])[CH3:19]>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.[Cu]I.C1COCC1.C(N(CC)CC)C>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:22]#[C:21][Si:18]([CH3:20])([CH3:19])[CH3:17])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a 250-mL pressure tube, 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (11.9 g, 42.3 mmol; Intermediate 1), Pd(Ph3P)2Cl2 (1.48 g, 0.05 mmol), CuI (0.8 g, 4.2 mmol) and THF/triethylamine (5:1, 85 mL) were added. This mixture was degassed with three vacuum/N2 cycles, and then trimethylsilylacetylene (9 mL, 63.5 mmol) was added. The pressure tube was sealed and heated at 80° C. for 2 days. Upon completion by LCMS, the reaction mixture was cooled down to room temperature and filtered through Celite with ethyl acetate (200 mL). The filtrate was concentrated to give the crude product that was used directly in the next step. LCMS: 299 (M+H)+.

Workup

customThis mixture was degassed with three vacuum/N2 cycles
customThe pressure tube was sealed
temperatureUpon completion by LCMS, the reaction mixture was cooled down to room temperature
filtrationfiltered through Celite with ethyl acetate (200 mL)
concentrationThe filtrate was concentrated

Sources & evidence

ORD record: ord-15d714e887b74dadb25894b31679c65f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09399646B2

Reaction notes

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