Potassium Carbonate → (R)-6-((1-(1,3-dioxoisoindolin-2-yl)butan-2-yl)amino)-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrile

HRID 1620108ノート

反応式

HRID 1620108 の反応式
C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[C:15]([F:16])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[CH:23][CH:22]=[CH:21]3)[N:9]=1.[NH2:28][C@H:29]([CH2:42][CH3:43])[CH2:30][N:31]1[C:39](=[O:40])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]1=[O:41].C(=O)([O-])O.[Na+]>O1CCOCC1>[O:41]=[C:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:39](=[O:40])[N:31]1[CH2:30][C@H:29]([NH:28][C:8]1[C:15]([F:16])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[CH:23][CH:22]=[CH:21]3)[N:9]=1)[CH2:42][CH3:43]

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 866838496-Chloro-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrileHCID 86683878(R)-2-(2-aminobutyl)isoindoline-1,3-dione

生成物 1

HCID 86683877(R)-6-((1-(1,3-dioxoisoindolin-2-yl)butan-2-yl)amino)-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrile収率 19.7%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
140 °C

実験手順

Potassium carbonate (146 mg) and 6-chloro-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrile (63 mg) were added to a tube containing a 1,4-dioxane (2 ml) solution containing (R)-2-(2-aminobutyl)isoindoline-1,3-dione (60 mg) and the tube was sealed, followed by stirring with heating at 140° C. for 13 hours. The reaction solution was cooled, and a saturated aqueous sodium hydrogen carbonate solution was added, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled away under reduced pressure. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=3:2), and a yellow solid of (R)-6-((1-(1,3-dioxoisoindolin-2-yl)butan-2-yl)amino)-5-fluoro-2-(quinolin-6-ylamino)nicotinonitrile (20 mg) was thus obtained.

後処理

  1. customthe tube was sealed
  2. temperatureThe reaction solution was cooled
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. customThe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=3:2)

出典と根拠

ORDレコード
ord-008da3ef44c840f391246c8ff5f83c3a
出典データセット
uspto-grants-2014_07
特許番号
US08772320B2

反応ノート

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