Triethylamine → 6-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbonitrile

HRID 340058Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:17]=O)=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1.C([N:21](CC)CC)C.Cl.NO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>CC#N.O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:21])=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 6-bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbaldehyde (Preparation 1, 60 g, 194 mmol) in MeCN (1.5 L) was added triethylamine (68.5 mL, 485 mmol) and hydroxylamine hydrochloride (20 g, 291 mmol). The reaction was heated at 60° C. for 3 hours. The reaction was cooled to 0° C., further triethylamine (220 mL, 1.55 mol) was added and TFAA (109 mL, 776 mmol) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 2 hours. Water (2 L) was added to the reaction mixture and the resulting solid was collected by filtration. The solid was dissolved in DCM (1 L) and the resulting solution was washed with water (2×500 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to give the title compound as a white solid (58.59 g) in a 99% yield.

Workup

temperatureThe reaction was cooled to 0° C.
temperatureto warm to room temperature
filtrationthe resulting solid was collected by filtration
dissolutionThe solid was dissolved in DCM (1 L)
washthe resulting solution was washed with water (2×500 mL)
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-2fdd5b64e639447b8b4c1e799c6fce16
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895544B2

Reaction notes

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