Potassium Carbonate → 5-Fluoro-2-(1-isobutyl-1H-indazol-5-yloxy)-benzonitrile

HRID 909227Notes

Reaction equation

[CH2:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([OH:14])=[CH:11][CH:12]=2)[CH:7]=[N:6]1)[CH:2]([CH3:4])[CH3:3].C([O-])([O-])=O.[K+].[K+].F[C:22]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:23]=1[C:24]#[N:25]>CN(C=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:22]([O:14][C:10]2[CH:9]=[C:8]3[C:13](=[CH:12][CH:11]=2)[N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[N:6]=[CH:7]3)=[C:23]([CH:26]=1)[C:24]#[N:25]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 1-isobutyl-1H-indazol-5-ol (2.33 g, 12.2 mmol) and K2CO3 (2.03 g, 14.7 mmol) in DMF (75 mL) was added 2,5-difluorobenzonitrile (1.87 g. 13.5 mmol). The mixture was heated to 110° C. for 18 hours under N2 atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane. The solution was washed with 1N HCl, filtered, and concentrated under reduced pressure. The residue was chromatographed on Biotage eluting with hexanes/ether (5:2) to afford 3.05 g of pale yellow oil (81% yield).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
dissolutionthe residue was dissolved in dichloromethane
washThe solution was washed with 1N HCl
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was chromatographed on Biotage
washeluting with hexanes/ether (5:2)

Sources & evidence

ORD record: ord-f943d1afb8bf491fa8006ff1fca09ed7
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017641B2

Reaction notes

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