Cesium carbonate → 1-Piperazinecarboxylic acid, 4-(3-cyano-7-quinolinyl)-3-oxo-, 1,1-dimethylethyl ester

HRID 1465748Notes

Reaction equation

HRID 1465748 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]#[N:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[O:62]=[C:63]1[NH:68][CH2:67][CH2:66][N:65]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[CH2:64]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:12]([C:7]1[CH:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([N:68]1[CH2:67][CH2:66][N:65]([C:69]([O:71][C:72]([CH3:74])([CH3:73])[CH3:75])=[O:70])[CH2:64][C:63]1=[O:62])[CH:11]=2)#[N:13]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 71721309HCID 71721309, compound

Product 1

HCID 895265061-Piperazinecarboxylic acid, 4-(3-cyano-7-quinolinyl)-3-oxo-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a 25 mL flask was added a stir bar, 7-chloroquinoline-3-carbonitrile (0.15 g, 0.79 mmol), Pd2 dba3 (0.072 g, 0.08 mmol), Xantphos (0.090 g, 0.16 mmol), cesium carbonate (0.36 g, 1.13 mmol) and tert-butyl 3-oxopiperazine-1-carboxylate (0.31 g, 1.6 mmol). The resulting mixture was degassed and purged with N2 (3×). To the flask was added 1,4 dioxane (10 mL). The resulting reaction mixture was then refluxed at 100° C. for overnight. Analysis of the reaction mixture by LC indicated that reaction had gone to completion. The solution was concentrated in vacuo and the resulting crude was dissolved in EtOAc and washed with brine, then dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was then subjected for purification by silica gel column chromatography (10% MeOH in DCM) to provide the title product.

Workup

  1. additionTo a 25 mL flask was added a stir bar
  2. customThe resulting mixture was degassed
  3. custompurged with N2 (3×)
  4. additionTo the flask was added 1,4 dioxane (10 mL)
  5. customThe resulting reaction mixture
  6. customAnalysis of the reaction mixture by LC indicated that reaction
  7. concentrationThe solution was concentrated in vacuo
  8. dissolutionthe resulting crude was dissolved in EtOAc
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude residue was then subjected for purification by silica gel column chromatography (10% MeOH in DCM)

Sources & evidence

ORD record
ord-67877752856940e0b22c4bd0be1634f0
Source dataset
uspto-grants-2015_04
Patent number
US08999991B2

Reaction notes

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