1,1'-Carbonyldiimidazole → 5-[1-(1-Methyl-1H-indol-3-yl)-2,2,2-trifluoro-1-hydroxyethyl]indazole-1-carboxylic acid cyclobutyl ester

HRID 244420Notes

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].[C:26](N1C=CN=C1)(N1C=CN=C1)=[O:27].[CH:38]1([OH:42])[CH2:41][CH2:40][CH2:39]1>N1C=CC=CC=1>[CH:38]1([O:42][C:26]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([C:3]([C:5]4[C:13]5[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=5)[N:7]([CH3:14])[CH:6]=4)([OH:4])[C:2]([F:1])([F:24])[F:25])=[CH:23][CH:22]=3)[CH:18]=[N:19]2)=[O:27])[CH2:41][CH2:40][CH2:39]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanol (0.142 mmol) and carbonyldiimidazole (0.185 mmol) in 1 mL of pyridine was heated at 80° C. for 10 hours, cooled to room temperature, and cyclobutanol (1.4 mmol) was added. The mixture was stirred overnight. The volatiles were removed and the residue purified by flash silica gel chromatography using 33% ethyl acetate in hexanes. The product-rich fractions were concentrated in vacuo to provide 0.076 mmol of the desired compound, m.p. 82° C.-84° C.

Workup

temperaturecooled to room temperature
customThe volatiles were removed
customthe residue purified by flash silica gel chromatography
concentrationThe product-rich fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-54aebfaef37247b9a8c92cfd356e3117
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658637B2

Reaction notes

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