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Cesium carbonate → 1-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile

HRID 714815
Notes
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Reaction equation

HRID 714815 reaction equation
[CH:1]1([C:4]2([C:10]#[N:11])[CH2:8][CH2:7][NH:6][C:5]2=[O:9])[CH2:3][CH2:2]1.[Cl:12][C:13]1[N:18]=[C:17](Cl)[CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[Cl:12][C:13]1[N:18]=[C:17]([N:6]2[CH2:7][CH2:8][C:4]([CH:1]3[CH2:3][CH2:2]3)([C:10]#[N:11])[C:5]2=[O:9])[CH:16]=[CH:15][N:14]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 775312,4-DichloropyrimidineHCID 916186313-Cyclopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178398021-(2-Chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrileYield 76.7%

Reagents, catalysts & solvents 3

HCID 636044
1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)
Catalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (18 g) obtained in Step C of Example 103, 2,4-dichloropyrimidine (17 g), cesium carbonate (76 g) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (4.1 g) in tetrahydrofuran (300 mL) was added tris(dibenzylideneacetone)dipalladium(0) (2.1 g), and the mixture was stirred overnight at 85° C. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (23 g).

Workup

  1. customThe insoluble substance was removed by filtration through Celite
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-0407b204fb6046408ac3be18a6c0494b
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09187453B2

Reaction notes

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