Cesium carbonate → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-4-pyrimidinyl]-1-azetidinesulfonamide

HRID 1024834Notes

Reaction equation

HRID 1024834 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]([O:56][CH:57]2[CH2:62][O:61][CH:60]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[O:59][CH2:58]2)[N:53]=[C:52]([S:69][CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[C:73]([F:77])[C:72]=2[F:78])[N:51]=1>O1CCOCC1.C(Cl)Cl.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:78][C:72]1[C:73]([F:77])=[CH:74][CH:75]=[CH:76][C:71]=1[CH2:70][S:69][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]([O:56][CH:57]2[CH2:58][O:59][CH:60]([C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)[O:61][CH2:62]2)[N:53]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 450805661-AzetidinesulfonamideHCID 536283394-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine

Product 1

HCID 53628338N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-4-pyrimidinyl]-1-azetidinesulfonamide

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of azetidine-1-sulphonamide (420 mg), tris(dibenzylideneacetone)dipalladium (0) (71 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (37 mg), cesium carbonate (380 mg) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine (350 mg) in anhydrous dioxane (8 ml) was heated to reflux in a microwave at 100° C., 300 W, open vessel with cooling for 10 minutes. The reaction mixture was diluted with methylene chloride, filtered through arbocel and the filtrate evaporated. The residue was purified by column chromatography on silica using a 80:20 to 70:30 mixture of iso-hexane and ethyl acetate as eluent to give the sub-title compound as a white solid.

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 10 minutes
  3. filtrationfiltered through arbocel
  4. customthe filtrate evaporated
  5. customThe residue was purified by column chromatography on silica using a 80:20
  6. additionto 70:30 mixture of iso-hexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-d8f75c274d104145a1d27450f17cd170
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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