Cyclobutanecarbonyl chloride → Cyclobutyl-{5-[2,2,2-trifluoro-1-hydroxy-1-(1-methyl-1H-indol-3-yl)ethyl]indazol-1-yl}methanone

HRID 244415Notes

Reaction equation

[F:1][C:2]([F:25])([F:24])[C:3]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][N:19]=[CH:18]2)([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH3:14])[CH:6]=1)[OH:4].[CH:26]1([C:30](Cl)=[O:31])[CH2:29][CH2:28][CH2:27]1>N1C=CC=CC=1.CCOCC.O>[CH:26]1([C:30]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([C:3]([OH:4])([C:5]4[C:13]5[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=5)[N:7]([CH3:14])[CH:6]=4)[C:2]([F:1])([F:24])[F:25])=[CH:23][CH:22]=3)[CH:18]=[N:19]2)=[O:31])[CH2:29][CH2:28][CH2:27]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanol (0.122 mmol) and cyclobutanecarbonyl chloride (0.159 mmol) in 1 mL pyridine was heated at 100° C. for 1.5 hours, cooled to room temperature and diluted with ether and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The volatiles were removed in vacuo and the residue purified by flash silica gel chromatography using 25% ethyl acetate in hexanes. The product-rich fractions were concentrated in vacuo to afford 0.091 mmol of the title compound, m.p. 79° C.-81° C.

Workup

temperaturecooled to room temperature
washThe organic layer was washed with water and brine
dry with materialdried over magnesium sulfate
customThe volatiles were removed in vacuo
customthe residue purified by flash silica gel chromatography
concentrationThe product-rich fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-6210037021d74012865cf784ae8b15fc
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658637B2

Reaction notes

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