Cesium carbonate → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide

HRID 1024906Notes

Reaction equation

HRID 1024906 reaction equation
[N:1]1([S:5]([NH2:8])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].ClC1C=C(OC2COC(C3C=CC=CC=3)OC2)N=C(SCC2C=CC=C(F)C=2F)N=1.Cl[C:46]1[CH:51]=[C:50]([O:52][C@@H:53]([C@H:55]2[CH2:59][O:58][C:57]([CH3:61])([CH3:60])[O:56]2)[CH3:54])[N:49]=[C:48]([S:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([F:70])[C:65]=2[F:71])[N:47]=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:71][C:65]1[C:66]([F:70])=[CH:67][CH:68]=[CH:69][C:64]=1[CH2:63][S:62][C:48]1[N:47]=[C:46]([NH:8][S:5]([N:1]2[CH2:4][CH2:3][CH2:2]2)(=[O:7])=[O:6])[CH:51]=[C:50]([O:52][C@@H:53]([C@H:55]2[CH2:59][O:58][C:57]([CH3:60])([CH3:61])[O:56]2)[CH3:54])[N:49]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 450805661-AzetidinesulfonamideHCID 536283394-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidineHCID 866198804-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

Product 1

HCID 53628360N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]-4-pyrimidinyl]-1-azetidinesulfonamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of azetidine-1-sulphonamide (prepared according to patent WO 2004/011443, 0.20 g), tris(dibenzylideneacetone)-dipalladium (0) (33 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-diphenyl (XPHOS) (17 mg), cesium carbonate (0.18 g) and 4-chloro-2-[[(2,3-difluorophenyl)-methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine (the product of step v) (0.15 g) in dioxane (5 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 25 min. Saturated aqueous ammonium chloride was added and the resulting mixture extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/isohexane (1:19 to 3:7 gradient) as eluent to give the subtitle compound as a yellow oil. Yield: 0.14 g.

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 25 min
  3. extractionthe resulting mixture extracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-6e7f083df65e4e55abe8b22f68908dd0
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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