Isobutylene oxide → 5-Fluoro-2-[1-(2-hydroxy-2-methylpropyl)-1H-indazol-5-yloxy]-benzonitrile

HRID 909239Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].[H-].[Na+].[CH3:22][C:23]1([CH3:26])[CH2:25][O:24]1>CN(C=O)C.CCOCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:22][C:23]([OH:24])([CH3:26])[CH3:25])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 5-fluoro-2-(1H-indazol-5-yloxy)-benzonitrile (0.100 g, 0.395 mmol) in DMF (4 mL) was treated with NaH (0.022 g, 60%, 056 mmol) and stirred for 5 minutes. 2,2-Dimethyloxirane (0.035 g, 0.48 mmol) was added and the solution was stirred at room temperature for 1 hour. The reaction mixture was then heated to 80° C. for 1.5 hours. The solution was cooled to room temperature, diluted with ether (50 mL), washed with water (3×5 mL), brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed eluting with ethyl acetate/hexanes (1:1) to afford 0.070 g of product (47% yield).

Workup

stirringthe solution was stirred at room temperature for 1 hour
temperatureThe solution was cooled to room temperature
washwashed with water (3×5 mL), brine
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customThe residue was chromatographed
washeluting with ethyl acetate/hexanes (1:1)

Sources & evidence

ORD record: ord-585733aeef87427db6383082b1317ff5
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017641B2

Reaction notes

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