Ethyl Acetate → HCID 90052203, compound

HRID 2284816Notes

Reaction equation

HRID 2284816 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]#[C:10][CH2:11][CH2:12][CH2:13][N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])=[C:4]([NH:25][CH2:26][CH2:27][CH3:28])[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:24]=[C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:22](=[O:23])[N:14]1[CH2:13][CH2:12][CH2:11][C:10]#[C:9][C:5]1[C:6]([CH3:8])=[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][C:4]=1[NH:25][CH2:26][CH2:27][CH3:28]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 133964-AminobenzonitrileHCID 90051808HCID 90051808, compound

Product 1

HCID 90052203HCID 90052203, compoundYield 91.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
160 °C

Procedure

To a solution of 2-(5-(2-chloro-4-methyl-6-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (T3, 65 mg) in 1,4-dioxane (3 mL), 4-aminobenzonitrile (29 mg), cesium carbonate (133 mg), tris(dibenzylideneacetone)dipalladium(0) (30 mg) and 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene (38 mg) were added at room temperature, the reaction vessel was sealed, and then by using a microwave reaction system, the mixture was stirred at 160° C. for 20 minutes. 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. The obtained residue was purified by silica gel column chromatography (eluent, 90 to 50% hexane in ethyl acetate) to obtain 4-((5-(5-(1,3-dioxoisoindolin-2-yl)-1-pentyn-1-yl)-4-methyl-6-(propylamino)pyrimidin-2-yl)amino)benzonitrile (T4, 72 mg) as pale yellow solid.

Workup

  1. customthe reaction vessel was sealed
  2. customa microwave reaction system
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe insoluble matter was removed by filtration through Cerite
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 90 to 50% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-55874ce1a4f04baea418989291d1fad6
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

Loading…