Cesium carbonate → N-{1-[4-(Isoquinolin-3-ylamino)-benzenesulfonyl]-piperidin-4-yl}-acrylamide

HRID 337237Notes

Reaction equation

HRID 337237 reaction equation
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.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:50]1[CH:59]=[CH:58][C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[N:51]=1.[NH2:60][C:61]1[CH:66]=[CH:65][C:64]([S:67]([N:70]2[CH2:75][CH2:74][CH:73]([NH:76][C:77](=[O:80])[CH:78]=[CH2:79])[CH2:72][CH2:71]2)(=[O:69])=[O:68])=[CH:63][CH:62]=1>O1CCOCC1.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]>[CH:52]1[C:57]2[C:58](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:59]=[C:50]([NH:60][C:61]2[CH:62]=[CH:63][C:64]([S:67]([N:70]3[CH2:71][CH2:72][CH:73]([NH:76][C:77](=[O:80])[CH:78]=[CH2:79])[CH2:74][CH2:75]3)(=[O:68])=[O:69])=[CH:65][CH:66]=2)[N:51]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 119282-ChloroquinolineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 71618273N-[1-(4-Amino-benzenesulfonyl)-piperidin-4-yl]-acrylamide

Product 1

HCID 86674091N-{1-[4-(Isoquinolin-3-ylamino)-benzenesulfonyl]-piperidin-4-yl}-acrylamideYield 0.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Tris(dibenzylideneacetone)dipalladium (0) (0.05 g, 0.06 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.015 g, 0.03 mmol), cesium carbonate (0.5 g, 2.0 mmol) and 2-chloroquinoline (0.085 g, 0.52 mmol) were added sequentially to a stirred solution of N-[1-(4-amino-benzenesulfonyl)-piperidin-4-yl]-acrylamide in dry dioxane (5 ml) under a nitrogen atmosphere. The mixture was heated to 110° C. for 12 hours. After this time the mixture was cooled to room temperature, filtered through a pad of celite, the celite was washed with EtOAc (50 ml) and the filtrate was washed sequentially with citric acid (10% solution, 20 ml) and brine (20 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated. The resulting residue was purified by prep HPLC to give the title compound (0.002 g, 0.5% yield) as a white solid.

Workup

  1. temperatureAfter this time the mixture was cooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. washthe celite was washed with EtOAc (50 ml)
  4. washthe filtrate was washed sequentially with citric acid (10% solution, 20 ml) and brine (20 ml)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by prep HPLC

Sources & evidence

ORD record
ord-5a056d78a55a45b3951f9735550cfac0
Source dataset
uspto-grants-2014_11
Patent number
US08889716B2

Reaction notes

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