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

HRID 534739ノート

反応式

HRID 534739 の反応式
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:53][C:54]1[CH:60]=[CH:59][C:57]([NH2:58])=[CH:56][CH:55]=1.Cl[C:62]1[N:67]=[CH:66][C:65]([C:68]([N:70]([CH3:92])[C:71]2[CH:76]=[CH:75][C:74]([CH2:77][N:78]3[CH2:83][CH2:82][N:81]([C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[C@@H:80]([CH3:91])[CH2:79]3)=[CH:73][CH:72]=2)=[O:69])=[CH:64][CH:63]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:53][C:54]1[CH:60]=[CH:59][C:57]([NH:58][C:62]2[N:67]=[CH:66][C:65]([C:68]([N:70]([CH3:92])[C:71]3[CH:76]=[CH:75][C:74]([CH2:77][N:78]4[CH2:83][CH2:82][N:81]([C:84]([O:86][C:87]([CH3:89])([CH3:88])[CH3:90])=[O:85])[C@@H:80]([CH3:91])[CH2:79]4)=[CH:73][CH:72]=3)=[O:69])=[CH:64][CH:63]=2)=[CH:56][CH:55]=1

参加物

7

反応物 4

HCID 97314-FluoroanilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 592622291,1-Dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

生成物 1

HCID 592622221,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)amino]-3-pyridinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate収率 47.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

BINAP (0.041 g, 0.0654 mmol), cesium carbonate (0.213 g, 0.654 mmol) and palladium acetate (0.009 g, 0.0436 mmol) were combined in dioxane (1 mL) and sonicated for 1 h under an argon atmosphere. To the red mixture was added 4-fluoroaniline (0.053 g, 0.479 mmol) and 1,1-dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D54) (0.2 g, 0.436 mmol). The mixture was stirred at 60° C. for 1 h, the solvent was removed under vacuum and the residues partitioned between EtOAc and water. The EtOAc layer was dried and concentrated. The crude product was purified by chromatography. Elution with a 0-70% EtOAc/petroleum ether gradient yielded the title compound as a pale yellow oil (0.110 g). δH (CDCl3, 400 MHz) 8.10 (1H, m), 7.40 (1H, dd), 7.25 (3H, m), 7.02 (4H, m), 6.92 (1H, s), 6.43 (1H, d), 4.18 (1H, br.s), 3.80 (1H, d), 3.48 (3H, s), 3.48 (1H, d), 3.36 (1H, d), 3.10 (1H, td), 2.70 (1H, d), 2.52 (1H, d), 2.10 (1H, m), 1.98 (1H, m), 1.85 (1H, br.s), 1.45 (9H, s), 1.20 (3H, d). MS (ES): MH+ 534.3.

後処理

  1. customsonicated for 1 h under an argon atmosphere
  2. customthe solvent was removed under vacuum
  3. customthe residues partitioned between EtOAc and water
  4. dry with materialThe EtOAc layer was dried
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography
  7. washElution with a 0-70% EtOAc/petroleum ether gradient

出典と根拠

ORDレコード
ord-34ce6fe18c204da2a6829249ef5a6e25
出典データセット
uspto-grants-2014_10
特許番号
US08853218B2

反応ノート

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