Water → 4-((5-(5-(1,3-Dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-((4-fluorophenyl)amino)pyrimidin-2-yl)amino)benzonitrile

HRID 2284766Notes

Reaction equation

HRID 2284766 reaction equation
Cl[C:2]1[C:7]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:6][N:5]=[C:4]([NH:24][C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[N:3]=1.C(OCC)(=O)C.O.[F:40][C:41]1[CH:47]=[CH:46][C:44]([NH2:45])=[CH:43][CH:42]=1>O1CCOCC1.C(N(CC)CC)C>[O:23]=[C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21](=[O:22])[N:13]1[CH2:12][CH2:11][CH2:10][C:9]#[C:8][C:7]1[C:2]([NH:45][C:44]2[CH:46]=[CH:47][C:41]([F:40])=[CH:42][CH:43]=2)=[N:3][C:4]([NH:24][C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)=[N:5][CH:6]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 97314-FluoroanilineHCID 900521494-((4-Chloro-5-(5-(1,3-dioxoisoindolin-2-yl)-1-pentyn-1-yl)pyrimidin-2-yl)amino)benzonitrile

Product 1

HCID 900523024-((5-(5-(1,3-Dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-((4-fluorophenyl)amino)pyrimidin-2-yl)amino)benzonitrile

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 4-((4-chloro-5-(5-(1,3-dioxoisoindolin-2-yl)-1-pentyn-1-yl)pyrimidin-2-yl)amino)benzonitrile (J13, 41 mg) in 1,4-dioxane (1.5 mL), 4-fluoroaniline (79 μL) and triethylamine (115 μL) were added at room temperature, and the mixture was stirred at 95° C. for 2 hours in a sealed tube. The reaction mixture was cooled to room temperature, and then ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed successively with 1.0 mol/L aqueous hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid matter was washed with a mixed solvent of chloroform and methanol, and then dried under reduced pressure to obtain 4-((5-(5-(1,3-dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-((4-fluorophenyl)amino)pyrimidin-2-yl)amino)benzonitrile (J14, 32 mg) as pale green solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed successively with 1.0 mol/L aqueous hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. washThe obtained solid matter was washed with a mixed solvent of chloroform and methanol
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-7104e6fe1078445db38c6d9939ac438b
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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