Cesium carbonate → N-{2-[(2,3-Difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}piperidine-4-sulfonamide

HRID 1959092Notes

Reaction equation

HRID 1959092 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([S:7]([NH2:10])(=[O:9])=[O:8])[CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:52]1[CH:57]=[C:56]([O:58][CH3:59])[N:55]=[C:54]([S:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:63]=2[F:69])[N:53]=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]>[F:69][C:63]1[C:64]([F:68])=[CH:65][CH:66]=[CH:67][C:62]=1[CH2:61][S:60][C:54]1[N:53]=[C:52]([NH:10][S:7]([CH:4]2[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]2)(=[O:9])=[O:8])[CH:57]=[C:56]([O:58][CH3:59])[N:55]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 18351283Piperidine-4-sulfonamideHCID 866198774-Chloro-2-([(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine2×

Product 1

HCID 58277465N-{2-[(2,3-Difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}piperidine-4-sulfonamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of piperidine-4-sulfonamide (0.33 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.43 g) and, 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine (the product from example 35 step i), 0.4 g) in dioxane (20 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 2 h. The reaction mixture was then reduced in vacuo and the residue partitioned between DCM (100 ml) and H2O (100 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×100 ml). Organics were combined, dried (MgSO4) and reduced in vacuo and the resulting yellow residue was purified prep HPLC to give the title compound as a white solid. Yield 13 mg

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 2 h
  3. customthe residue partitioned between DCM (100 ml) and H2O (100 ml)
  4. customThe organics were separated
  5. extractionthe aqueous layer was re-extracted with DCM (2×100 ml)
  6. dry with materialdried (MgSO4)
  7. customthe resulting yellow residue was purified prep HPLC

Sources & evidence

ORD record
ord-0577548e013d49ee91456515e1629a35
Source dataset
uspto-grants-2013_04
Patent number
US08410123B2

Reaction notes

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