Hydrochloric Acid → 6-chloro-N5-(1-cyanocyclopropyl)-1-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

HRID 514269ノート

反応式

HRID 514269 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:15]([F:18])([F:17])[F:16])=[O:12])[NH:8]2)=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30].[CH:37]1(B(O)O)[CH2:39][CH2:38]1.C(=O)([O-])[O-].[Na+].[Na+].N1C=CC=CC=1C1C=CC=CN=1.Cl>CN(C)C=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:28])[F:27])[CH:20]=3)[C:15]([F:16])([F:18])[F:17])=[O:12])[N:8]2[CH:37]2[CH2:39][CH2:38]2)=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 14742,2'-BipyridineHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 867139856-chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

生成物 1

HCID 867139876-chloro-N5-(1-cyanocyclopropyl)-1-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide収率 6.7%

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

6-Chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.20 g, 0.34 mmol), cyclopropylboronic acid (0.063 g, 0.69 mmol) and sodium carbonate (0.074 g, 0.69 mmol) were initially charged as a suspension in N,N-dimethylformamide (1 ml), and a hot solution of copper(II) acetate (0.064 g, 0.34 mmol) and 2,2′-bipyridyl (0.054 g, 0.34 mmol) was added. The reaction mixture was stirred at 70° C. over 16 h. After cooling, hydrochloric acid (10 ml, 1 mol/l) was added and the organic phase was removed. The aqueous phase was extracted with ethyl acetate (3×) and the combined organic phases were washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.013 g (6% of theory) of 6-chloro-N5-(1-cyanocyclopropyl)-1-cyclopropyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

後処理

  1. temperatureAfter cooling
  2. customthe organic phase was removed
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. washthe combined organic phases were washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue is purified by means of preparative HPLC (Kromasil100, C18 250×20

出典と根拠

ORDレコード
ord-b10ab9aee39640d3a895b53bd726ecbb
出典データセット
uspto-grants-2015_08
特許番号
US09107411B2

反応ノート

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