Ethyl Acetate → 4-((5-(5-(1,3-Dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)benzonitrile

HRID 2284750Notes

Reaction equation

HRID 2284750 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[C:5]([C:13]#[C:14][CH2:15][CH2:16][CH2:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])=[CH:4][N:3]=1.[NH2:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:28]=[C:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:26](=[O:27])[N:18]1[CH2:17][CH2:16][CH2:15][C:14]#[C:13][C:5]1[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:7][C:2]([NH:29][C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 133964-AminobenzonitrileHCID 900517842-(5-(2-Chloro-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

Product 1

HCID 900522854-((5-(5-(1,3-Dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)benzonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tris(dibenzylideneacetone)dipalladium(0) (835 mg) and 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene (1.06 g) in 1,4-dioxane (125 mL), 2-(5-(2-chloro-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (H2, 3.60 g), 4-aminobenzonitrile (2.69 g) and cesium carbonate (8.90 g) were added at room temperature under a nitrogen atmosphere, and the mixture was stirred at 90° C. for 7 hours. The reaction mixture was cooled to room temperature, and then ethyl acetate was added to the reaction mixture. The insoluble matter was removed by filtration through Cerite, and then the solvent was evaporated under reduced pressure. To the obtained residue, water was added. The solid matter was taken by filtration, and washed with water to obtain 4-((5-(5-(1,3-dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-(pyrrolidin-1-yl)pyrimidin-2-yl)amino)benzonitrile (H3).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe insoluble matter was removed by filtration through Cerite
  3. customthe solvent was evaporated under reduced pressure
  4. additionTo the obtained residue, water was added
  5. filtrationThe solid matter was taken by filtration
  6. washwashed with water

Sources & evidence

ORD record
ord-855e87cb05d44e34958e0f302f420dd1
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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