Cesium carbonate → HCID 59558831, compound

HRID 1958993Notes

Reaction equation

HRID 1958993 reaction equation
[N:1]1([S:5]([NH2:8])(=[O:7])=[O:6])[CH2:4][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:50]1[CH:55]=[C:54]([S:56][CH3:57])[N:53]=[C:52]([S:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[C:61]=2[F:67])[N:51]=1.[Cl-].[NH4+]>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:67][C:61]1[C:62]([F:66])=[CH:63][CH:64]=[CH:65][C:60]=1[CH2:59][S:58][C:52]1[N:51]=[C:50]([NH:8][S:5]([N:1]2[CH2:4][CH2:3][CH2:2]2)(=[O:7])=[O:6])[CH:55]=[C:54]([S:56][CH3:57])[N:53]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 450805661-AzetidinesulfonamideHCID 86619883HCID 86619883, compound2×

Product 1

HCID 59558831HCID 59558831, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of azetidine-1-sulfonamide (prepared according to patent WO 2004/011443, 0.32 g), tris(dibenzylideneacetone)-dipalladium (0) (33 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (17 mg), cesium carbonate (0.58 g) and 4-chloro-2-[(2,3-difluorobenzyl)thio]-6-(methylthio)pyrimidine (the product of example 57, step i) (0.38 g) in dioxane (10 mL) was heated at 100° C. for 18 h. The mixture was cooled and saturated ammonium chloride was added and the resulting mixture extracted with EtOAc. The combined organic extracts were washed with saturated aqueous sodium chloride, dried (MgSO4), filtered and evaporated. The residue was purified by reverse phase HPLC eluting with acetonitrile/aq. 0.1% ammonium acetate mixtures to give the title compound as a white solid. Yield: 50 mg.

Workup

  1. temperatureThe mixture was cooled
  2. extractionthe resulting mixture extracted with EtOAc
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by reverse phase HPLC
  8. washeluting with acetonitrile/aq

Sources & evidence

ORD record
ord-815616f707cc41f4bd08eec4030124ab
Source dataset
uspto-grants-2013_04
Patent number
US08410123B2

Reaction notes

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