Water → HCID 178502381、化合物

HRID 1500513ノート

反応式

HRID 1500513 の反応式
[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].Br[C:38]1[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][C:39]=1[O:45][C:46]([F:49])([F:48])[F:47].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:38]3[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][C:39]=3[O:45][C:46]([F:47])([F:48])[F:49])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 141291984-Bromo-3-(trifluoromethoxy)anilineHCID 178502353HCID 178502353、化合物

生成物 1

HCID 178502381HCID 178502381、化合物収率 53%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

To a solution of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (1.80 g, 3.63 mmol) and 4-bromo-3-trifluoromethoxy-phenylamine (1.00 g, 3.90 mmol) dissolved in toluene (5.4 mL) and water (2.7 mL) was added potassium carbonate (2.50 g, 18.1 mmol). The reaction mixture was sparged with nitrogen. Tetrakis(triphenylphosphine)-palladium(0) (0.21 g, 0.18 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. in a sealed tube overnight, diluted in ethyl acetate (100 mL) and washed with water, brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce a red paste (6.5 g), which was purified by silica gel chromatography (120 g silica, 0-3% MeOH/DCM) to provide the title intermediate (1.05 g) and a second fraction which was purified by reverse phase HPLC to provide the di-TFA salt of the title intermediate (800 mg). (Total yield 80%).

後処理

  1. customThe reaction mixture was sparged with nitrogen
  2. customthe reaction mixture was sparged with nitrogen
  3. additiondiluted in ethyl acetate (100 mL)
  4. washwashed with water, brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto produce a red paste (6.5 g), which
  9. customwas purified by silica gel chromatography (120 g silica, 0-3% MeOH/DCM)

出典と根拠

ORDレコード
ord-9ddbb592361b40ddb36551aab4146539
出典データセット
uspto-grants-2015_12
特許番号
US09206159B2

反応ノート

読み込み中…