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 418807ノート

反応式

HRID 418807 の反応式
[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

参加物

4

反応物 2

HCID 66321Lithium iodideHCID 576159421,1,1-Trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-[({6-methyl-1-[3-(methyloxy)phenyl]-1H-indazol-4-yl}amino)methyl]-2-pentanol

生成物 1

HCID 119926194-Fluoro-2-[4,4,4-trifluoro-3-hydroxy-3-({[1-(3-hydroxyphenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1-dimethylbutyl]phenol収率 31.7%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
220 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-aae009ef049f43aab7acd82f968ab792
出典データセット
uspto-grants-2012_01
特許番号
US08093281B2

反応ノート

読み込み中…