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

HRID 2406756노트

반응식

HRID 2406756 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
140 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-96773d466eb541019daf144777bde3bd
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809371B2

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