Acetic Acid → 3-Ethyl-1-(2-((4-(morpholin-4-yl)phenyl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714782Notes

Reaction equation

HRID 714782 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C:10]([CH2:15][CH3:16])([C:13]#[N:14])[C:9]2=[O:17])[CH:5]=[CH:4][N:3]=1.[N:18]1([C:24]2[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(O)(=O)C>C(O)CCC>[CH2:15]([C:10]1([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:28][C:27]3[CH:26]=[CH:25][C:24]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[CH:30][CH:29]=3)[N:7]=2)[C:9]1=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 1178407381-(2-Chloro-4-pyrimidinyl)-3-ethyl-2-oxo-3-pyrrolidinecarbonitrile

Product 1

HCID 1178404503-Ethyl-1-(2-((4-(morpholin-4-yl)phenyl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrileYield 45.6%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (42 mg) obtained in Step A, 4-(morpholin-4-yl)aniline (39 mg) and acetic acid (11 μL) in 1-butanol (2 mL) was stirred in a microwave reactor at 160° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, to the residue was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and recrystallized (hexane/ethyl acetate) to give the title compound (30 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, to the residue
  2. additionwas added saturated aqueous sodium hydrogen carbonate solution
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  8. customrecrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-94fc1a293f294443acb47aae939b42f9
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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