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

HRID 1620108Notes

Reaction equation

HRID 1620108 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-008da3ef44c840f391246c8ff5f83c3a
Source dataset
uspto-grants-2014_07
Patent number
US08772320B2

Reaction notes

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