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

HRID 714788Notes

Reaction equation

HRID 714788 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C:10]([CH:15]([CH3:17])[CH3:16])([C:13]#[N:14])[C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.[N:19]1([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(O)(=O)C>C(O)CCC>[CH: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:29][C:28]3[CH:27]=[CH:26][C:25]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[CH:31][CH:30]=3)[N:7]=2)[C:9]1=[O:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 1178405011-(2-Chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178403133-Isopropyl-1-(2-((4-(morpholin-4-yl)phenyl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrileYield 35.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step C, 4-(morpholin-4-yl)aniline (77 mg) and acetic acid (25 jL) 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, saturated aqueous sodium hydrogen carbonate solution was added thereto, 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 (54 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution
  2. additionwas added
  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-2e700f6d59cc4a8ca8f277979e64430c
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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