Cesium carbonate → tert-Butyl 4-(6-cyano-7-methylquinolin-2-yl)-3-oxopiperazine-1-carboxylate

HRID 1465737Notes

Reaction equation

HRID 1465737 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([CH3:14])=[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:63]=[C:64]1[NH:69][CH2:68][CH2:67][N:66]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:65]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][C:6]=1[CH3:14])[N:3]=[C:2]([N:69]1[CH2:68][CH2:67][N:66]([C:70]([O:72][C:73]([CH3:75])([CH3:74])[CH3:76])=[O:71])[CH2:65][C:64]1=[O:63])[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 895253462-Chloro-7-methylquinoline-6-carbonitrile

Product 1

HCID 131732663tert-Butyl 4-(6-cyano-7-methylquinolin-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-Chloro-7-methylquinoline-6-carbonitrile (0.2 g, 0.98 mmol), Pd2 dba3 (0.11 g, 0.19 mmol), Xantphos (0.090 g, 0.090 mmol), Cesium Carbonate (0.26 g, 0.63 mmol) and tert-Butyl 3-oxopiperazine-1-carboxylate (0.29 g, 1.4 mmol). The resulting mixture was degassed and purged with N2 three times. To the flask was added 1,4-dioxane (4 mL). The reaction mixture was then refluxed at 100° C. overnight. 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 then purified by silica gel column chromatography (10% MeOH in DCM) to provide the title compound.

Workup

  1. additionTo a 25 mL flask was added a stir bar
  2. customThe resulting mixture was degassed
  3. custompurged with N2 three times
  4. additionTo the flask was added 1,4-dioxane (4 mL)
  5. concentrationThe solution was concentrated in vacuo
  6. dissolutionthe resulting crude was dissolved in EtOAc
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was then purified by silica gel column chromatography (10% MeOH in DCM)

Sources & evidence

ORD record
ord-d627c96d866d43179acc01b184130c0a
Source dataset
uspto-grants-2015_04
Patent number
US08999991B2

Reaction notes

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