Bromotrimethylsilane → 2-(4-Bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile

HRID 626755Notes

Reaction equation

[Cl:1][C:2]1[C:3]([N:10]2[CH:20]=[C:13]3[C:14](Cl)=[N:15][CH:16]=[C:17]([F:18])[C:12]3=[N:11]2)=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[Br:21][Si](C)(C)C>C(#N)CC>[Br:21][C:14]1[C:13]2=[CH:20][N:10]([C:3]3[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:4]=3[C:5]#[N:6])[N:11]=[C:12]2[C:17]([F:18])=[CH:16][N:15]=1

Participants

Conditions

Temperature: 110 °C

Procedure

3-Chloro-2-(4-chloro-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-benzonitrile (890 mg, 2.9 mmol) was suspended in propionitrile (30 mL), under an atmosphere of nitrogen and bromotrimethylsilane (2.0 mL, 15 mmol) was added. The reaction mixture was heated at 110° C. for 3.5 hours. The resultant mixture was cooled to room temperature and partitioned between ethyl acetate and 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. The residue was triturated with diethyl ether to afford the title compound as a yellow solid (980 mg, 96% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.54 (d, J=2.5 Hz, 1H), 8.25-8.21 (m, 3H), 7.94 (t, J=8.1 Hz, 1H).

Workup

custompartitioned between ethyl acetate and 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
customThe residue was triturated with diethyl ether

Sources & evidence

ORD record: ord-cc36a3099d1544d4b17b8bdb1968e209
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Reaction notes

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