Water → HCID 178502394、化合物

HRID 1411350ノート

反応式

HRID 1411350 の反応式
Br[C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20].C1(C)C=CC=CC=1.O.C(=O)([O-])[O-].[K+].[K+]>[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>[CH3:14][O:15][C:16](=[O:49])[NH:17][C@H:18]([C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:35]=[CH:36][C:37]([C:2]3[CH:3]=[C:4]([F:13])[C:5]([NH2:6])=[CH:7][C:8]=3[C:9]([F:12])([F:11])[F:10])=[CH:38][CH:39]=2)[N:33]=1)=[O:23])[CH:19]([CH3:21])[CH3:20]

参加物

7

反応物 5

HCID 962WaterHCID 1140TolueneHCID 11430Potassium CarbonateHCID 70180464-Bromo-2-fluoro-5-(trifluoromethyl)anilineHCID 178502353HCID 178502353、化合物

生成物 1

HCID 178502394HCID 178502394、化合物収率 77.4%

試薬・触媒・溶媒 1

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒

反応条件

温度
100 °C

実験手順

A mixture of 4-bromo-2-fluoro-5-(trifluoromethyl)aniline (78 mg, 0.302 mmol) and [(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 (150 mg, 0.302 mmol) in toluene (0.6 mL, 6 mmol) and water (0.4 mL, 20 mmol) was purged with nitrogen. Potassium carbonate (208.8 g, 1.511 mmol) and tetrakis(triphenylphosphine)-palladium(0) (35 mg, 0.030 mmol) were added under an atmosphere of nitrogen. The reaction mixture was capped and heated at 100° C. overnight, cooled to RT, and partitioned between ethyl acetate (5.0 mL) and water (1.5 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated to give a yellowish oil, which was purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes). Desired fractions were combined and concentrated to give the title intermediate as a yellowish solid (128 mg, 77% yield). (m/z): [M+H]+ calcd for C27H24F4N5O3 548.22 found 548.6.

後処理

  1. customwas purged with nitrogen
  2. customThe reaction mixture was capped
  3. temperaturecooled to RT
  4. custompartitioned between ethyl acetate (5.0 mL) and water (1.5 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellowish oil, which
  9. customwas purified by silica gel chromatography (12 g silica gel, 0-100% EtOAc/hexanes)
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-00a25c4ae2fd40e0a9e5abae3b2c235c
出典データセット
uspto-grants-2014_12
特許番号
US08921372B2

反応ノート

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