3-Aminopyridine → 3-Ethyl-2-oxo-1-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyrrolidine-3-carbonitrile dihydrochloride

HRID 714807Notes

Reaction equation

HRID 714807 reaction equation
[Cl:1][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.[NH2:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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]>[ClH:1].[ClH:1].[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:18][C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[N:7]=2)[C:9]1=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 1178407381-(2-Chloro-4-pyrimidinyl)-3-ethyl-2-oxo-3-pyrrolidinecarbonitrile

Product 1

HCID 1178411193-Ethyl-2-oxo-1-(2-(pyridin-3-ylamino)pyrimidin-4-yl)pyrrolidine-3-carbonitrile dihydrochlorideYield 64.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step A of Example 2, 3-aminopyridine (45 mg), cesium carbonate (260 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (37 mg) in tetrahydrofuran (2 mL) was added tris(dibenzylideneacetone)dipalladium(0) (37 mg), and the mixture was stirred overnight at 90° 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 (NH, hexane/ethyl acetate), 4M hydrogen chloride in ethyl acetate (4 mL) was added thereto, and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the residue was recrystallized (ethyl acetate) to give the title compound (49 mg).

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 (NH, hexane/ethyl acetate), 4M hydrogen chloride in ethyl acetate (4 mL)
  4. additionwas added
  5. stirringthe mixture was stirred at room temperature for 5 min
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was recrystallized (ethyl acetate)

Sources & evidence

ORD record
ord-3492af82b2c84db4b1661f5715fd97b9
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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