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

HRID 534736ノート

反応式

HRID 534736 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]2[CH: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.[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[OH:40].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[O:40][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:32])[C:11]2[CH: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

参加物

6

反応物 3

HCID 97072-FluorophenolHCID 11430Potassium CarbonateHCID 592622291,1-Dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

生成物 1

HCID 592622161,1-Dimethylethyl (2S)-4-({4-[({6-[(2-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate収率 32.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
80 °C

実験手順

1,1-Dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D54) (0.1 g, 0.218 mmol) and 2-fluorophenol (0.025 g, 0.436 mmol) were dissolved in DMF (5 mL). Potassium carbonate (0.06 g, 0.436 mmol) was added and the mixture was heated to 80° C. overnight then at 130° C. for 7 h. The mixture was left to stand at room temperature overnight and the solvent removed under vacuum. The residue was partitioned between EtOAc and water. The organic layer was dried and concentrated to produce a brown oil. The crude product was purified by MDAP to yield the formic acid salt. The salt was taken up in DCM and washed with sat. NaHCO3. The DCM layer was dried and concentrated to yield the title compound as a colourless oil (0.038 g). δH (CDCl3, 400 MHz) 8.02 (1H, d), 7.68 (1H, dd), 7.23 (2H, d), 7.15 (4H, m), 6.98 (2H, d), 6.78 (1H, d), 4.18 (1H, br.s), 3.80 (1H, d), 3.48 (3H, s), 3.46 (1H, d), 3.33 (1H, d), 3.08 (1H, td), 2.69 (1H, d), 2.51 (1H, d), 2.10 (1H, dd), 1.98 (1H, m), 1.46 (9H, s), 1.20 (3H, d). MS (ES): MH+ 535.3.

後処理

  1. waitThe mixture was left
  2. waitto stand at room temperature overnight
  3. customthe solvent removed under vacuum
  4. customThe residue was partitioned between EtOAc and water
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customto produce a brown oil
  8. customThe crude product was purified by MDAP
  9. customto yield the formic acid salt
  10. washwashed with sat. NaHCO3
  11. dry with materialThe DCM layer was dried
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-ae91dddc8b4541a988d815f0ef1c027d
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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