Bromotrimethylsilane → 4-Bromo-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

HRID 626796Notes

Reaction equation

Cl[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1.[Br:20][Si](C)(C)C>C(#N)CC.C(OCC)(=O)C>[Br:20][C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([F:19])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

4-Chloro-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (3.05 g, 10.1 mmol) was suspended in propionitrile (60 mL) under an atmosphere of nitrogen and bromotrimethylsilane (4.0 mL, 30.0 mmol) was added. The reaction mixture was heated at 100° C. overnight. The resultant mixture was cooled to room temperature, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound as a beige solid (3.5 g, 100% yield). This was used directly in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 9.46 (d, J=2.5 Hz, 1H), 8.21 (d, J=3.4 Hz, 1H), 7.85-7.77 (m, 1H), 7.74-7.64 (m, 2H).

Workup

washwashed with saturated aqueous sodium bicarbonate solution
customThe layers were separated
washthe organic layer was washed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-0d70136bd43446aa82a3f3a6377fb568
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Reaction notes

Loading…