Cesium carbonate → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]-4-pyrimidinyl]azetidine-1-sulphonamide

HRID 1175340Notes

Reaction equation

HRID 1175340 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][CH:9]2[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11][CH2:10]2)[N:5]=[C:4]([S:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=2[F:26])[N:3]=1.[N:27]1([S:31]([NH2:34])(=[O:33])=[O:32])[CH2:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+]>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:26][C:20]1[C:21]([F:25])=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][S:17][C:4]1[N:3]=[C:2]([NH:34][S:31]([N:27]2[CH2:30][CH2:29][CH2:28]2)(=[O:33])=[O:32])[CH:7]=[C:6]([CH2:8][CH:9]2[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11][CH2:10]2)[N:5]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 450805661-AzetidinesulfonamideHCID 866198634-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]pyrimidine

Product 1

HCID 53628340N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]-4-pyrimidinyl]azetidine-1-sulphonamide

Reagents, catalysts & solvents 2

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

Procedure

A solution of the product of step i) (109 mg), tris(dibenzylideneacetone)dipalladium(0) (14 mg), azetidine-1-sulphonamide (145 mg), 2-dicyclohexyl-phosphino-2′,4′,6′-tri-isopropyl,1,1′-biphenyl (XPHOS)(14 mg) and cesium carbonate (120 mg) in anhydrous dioxane (2.3 ml) was heated at 100° C. for 45 min. The reaction mixture was partitioned between ethyl acetate and water. Acetic acid (0.2 ml) was added and the separated organic phase was washed with water and brine, dried (MgSO4) and the solvent evaporated under reduced pressure. The residue was purified by flash silica-gel chromatography eluting with 40% ethyl acetate in iso-hexane to give the sub-title compound as a yellow viscous oil.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. additionAcetic acid (0.2 ml) was added
  3. washthe separated organic phase was washed with water and brine
  4. dry with materialdried (MgSO4)
  5. customthe solvent evaporated under reduced pressure
  6. customThe residue was purified by flash silica-gel chromatography
  7. washeluting with 40% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-ccc15f76f56b47d0a2591c2a7e428ba4
Source dataset
uspto-grants-2010_11
Patent number
US07838675B2

Reaction notes

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