Lithium iodide → 4-Fluoro-2-[4,4,4-trifluoro-3-hydroxy-3-({[1-(3-hydroxyphenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1-dimethylbutyl]phenol

HRID 418807Notes

Reaction equation

[F:1][C:2]([F:39])([F:38])[C:3]([CH2:18][NH:19][C:20]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]2[C:21]=1[CH:22]=[N:23][N:24]2[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36]C)[CH:31]=1)([OH:17])[CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15]C)([CH3:7])[CH3:6].[I-].[Li+]>CN1CCCC1=O>[F:14][C:12]1[CH:11]=[CH:10][C:9]([OH:15])=[C:8]([C:5]([CH3:7])([CH3:6])[CH2:4][C:3]([OH:17])([CH2:18][NH:19][C:20]2[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]3[C:21]=2[CH:22]=[N:23][N:24]3[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)[C:2]([F:1])([F:38])[F:39])[CH:13]=1

Participants

Conditions

Temperature: 220 °C

Procedure

A mixture of 1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-[({6-methyl-1-[3-(methyloxy)phenyl]-1H-indazol-4-yl}amino)methyl]-2-pentanol (Example 22, 137 mg, 0.25 mmol) and lithium iodide (1 g, 7.5 mmol) in N-methylpyrrolidinone (6 mL) was heated in a microwave at 220° C. for 55 minutes. The solvent was removed using a vacuum centrifuge and the residue was partitioned between water (25 mL) and dichloromethane (50 mL) and passed through a hydrophobic frit. The organic filtrate was evaporated under reduced pressure and purified by silica gel chromatography (20 g cartridge) eluting with a 100:0 to 0:100 gradient of cyclohexane:ethyl acetate over 30 minutes to give the title compound (41 mg).

Workup

customThe solvent was removed
customthe residue was partitioned between water (25 mL) and dichloromethane (50 mL)
customThe organic filtrate was evaporated under reduced pressure
custompurified by silica gel chromatography (20 g cartridge)
washeluting with a 100:0 to 0:100 gradient of cyclohexane

Sources & evidence

ORD record: ord-aae009ef049f43aab7acd82f968ab792
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093281B2

Reaction notes

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