Water → HCID 24852376, compound

HRID 2244639Notes

Reaction equation

[F:1][CH:2](O)[CH2:3][CH2:4][F:5].[H-].[Na+].[Cl:9][C:10]1[CH:11]=[C:12]([C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4[CH2:31][C:32]([NH2:34])=[O:33])[N:18]=2)[CH:13]=[CH:14][C:15]=1F.[OH2:35]>CN(C=O)C>[Cl:9][C:10]1[CH:11]=[C:12]([C:17]2[O:21][N:20]=[C:19]([C:22]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4[CH2:31][C:32]([NH2:34])=[O:33])[N:18]=2)[CH:13]=[CH:14][C:15]=1[O:35][CH:3]([CH2:4][F:5])[CH2:2][F:1]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of 1,3-difluoropropanol (62 mg) in DMF (2.4 ml) was added 60% NaH (19 mg) at −10° C., followed by stirring at −10° C. for 0.5 hour. To this reaction mixture was added 2-{4-[5-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1H-indol-1-yl}acetamide (120 mg) at −10° C., followed by stirring at −10° C. for 3 hours. After adding water to the reaction solution, the reaction mixture was extracted with EtOAc, the organic layer was washed with saturated brine, dried over anhydrous MgSO4, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:CH3OH=100:0 to 95:5) to obtain 2-[4-(5-{3-chloro-4-[2-fluoro-1-(fluoromethyl)ethoxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]acetamide (76.9 mg) as a white solid.

Workup

stirringby stirring at −10° C. for 3 hours
extractionthe reaction mixture was extracted with EtOAc
washthe organic layer was washed with saturated brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (chloroform:CH3OH=100:0 to 95:5)

Sources & evidence

ORD record: ord-1c39484978fa42048fa104d27d66855e
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678820B2

Reaction notes

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