Cesium carbonate → tert-Butyl 4-(6-cyanoquinolin-2-yl)-3-oxopiperazine-1-carboxylate

HRID 1465733Notes

Reaction equation

HRID 1465733 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]#[N:13])[CH:8]=2)[N: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]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N: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]=[CH:10]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 112524682-Chloroquinoline-6-carbonitrile

Product 1

HCID 131732662tert-Butyl 4-(6-cyanoquinolin-2-yl)-3-oxopiperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a 25 mL flask was added a stir bar, 2-chloroquinoline-6-carbonitrile (0.015 g, 0.79 mmol), Pd2 dba3 (0.072 g, 0.08 mmol), Xantphos (0.09 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 reaction mixture was then refluxed at 100° C. 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, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified 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. customAnalysis of the reaction mixture by LC indicated that reaction
  6. concentrationThe solution was concentrated in vacuo
  7. dissolutionthe resulting crude was dissolved in EtOAc
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was purified by silica gel column chromatography (10% MeOH in DCM)

Sources & evidence

ORD record
ord-39f5ec5f0ff042449979f97d353b15d4
Source dataset
uspto-grants-2015_04
Patent number
US08999991B2

Reaction notes

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