1-(benzyloxymethyl)-2-phenyl-1H-imidazole → 4-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104956ノート

反応式

HRID 2104956 の反応式
[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]C(CC)C.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]([F:45])=[C:33]([CH:44]=1)/[CH:34]=[N:35]/[C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1)[CH3:27]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([N:35]([CH2:34][C:33]2[CH:44]=[C:29]([O:28][CH2:26][CH3:27])[CH:30]=[C:31]([O:46][CH:47]([CH3:49])[CH3:48])[C:32]=2[F:45])[C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:13][N:12]=[C:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 578039651-(benzyloxymethyl)-2-phenyl-1H-imidazoleHCID 178418400CID 53628100HCID 178466720HCID 178466720、化合物

生成物 1

HCID 688133704-((1-(benzyloxymethyl)-2-phenyl-1H-imidazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile収率 24.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of Intermediate 15.1 (100 mg, 0.378 mmol) in 2 mL THF at 0° C., was added sec-BuLi (0.81 M in cyclohexane, 514 μL, 0.416 mmol). The mixture was stirred at 0° C. for 10 min, then a solution of Intermediate 7.3 (123 mg, 0.378 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at 0° C. for 30 min and rt 1 h, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient) followed by preparative HPLC purification to afford 53.7 mg of Intermediate 15.2.

後処理

  1. stirringThe mixture was stirred at 0° C. for 30 min and rt 1 h
  2. customwas quenched with sat. NH4Cl
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0 to 75% EtOAc/hexanes gradient)
  8. customfollowed by preparative HPLC purification

出典と根拠

ORDレコード
ord-f2d3969455624f90b068529c099f105f
出典データセット
uspto-grants-2009_08
特許番号
US07576098B2

反応ノート

読み込み中…