4-Fluorophenol → 1,1-Dimethylethyl (2S)-4-({6-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 644758ノート

反応式

HRID 644758 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]2[N:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]3)=[CH:13][CH:12]=2)=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:39][C:40]1[CH:45]=[CH:44][C:43]([OH:46])=[CH:42][CH:41]=1>CN(C=O)C>[F:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][C:2]2[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]3[N:16]=[CH:15][C:14]([CH2:17][N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]4)=[CH:13][CH:12]=3)=[O:9])=[CH:4][CH:3]=2)=[CH:42][CH:41]=1

参加物

5

反応物 3

HCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 592622351,1-Dimethylethyl (2S)-4-({6-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate

生成物 1

HCID 592622071,1-Dimethylethyl (2S)-4-({6-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate収率 33.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
130 °C

実験手順

To 1,1-dimethylethyl (2S)-4-({6-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylate (D106) (0.139 g, 0.303 mmol) in DMF (4 mL) under an argon atmosphere was added potassium carbonate (0.293 g, 0.212 mmol) and 4-fluorophenol (0.169 g, 1.51 mmol). The reaction mixture was stirred and heated at 130° C. for 5 h then concentrated in vacuo. The residue was re-dissolved in DCM/water. The organic layer was washed with 2M NaOH solution and brine then dried (Na2SO4) and concentrated to give the crude product which was purified by column chromatography. Elution with EtOAc/DCM gave the title compound as a colourless oil (0.054 g). MS (ES): MH+ 536.2.

後処理

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in DCM/water
  3. washThe organic layer was washed with 2M NaOH solution and brine
  4. dry with materialthen dried (Na2SO4)
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by column chromatography
  8. washElution with EtOAc/DCM

出典と根拠

ORDレコード
ord-32af8c62219348de93ead8694ebf40ef
出典データセット
uspto-grants-2010_04
特許番号
US07700599B2

反応ノート

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