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 418807노트

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HRID 418807 반응식
[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

참가 물질

4

반응물 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

생성물 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]phenol수율 31.7%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
220 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-aae009ef049f43aab7acd82f968ab792
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093281B2

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