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

HRID 1024911Notes

Reaction equation

HRID 1024911 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+].ClC1C=C(OC2COC(C3C=CC=CC=3)OC2)N=C(SCC2C=CC=C(F)C=2F)N=1.Cl[C:80]1[CH:85]=[C:84]([O:86][C@@H:87]([C@@H:89]2[CH2:93][O:92][C:91]([CH3:95])([CH3:94])[O:90]2)[CH3:88])[N:83]=[C:82]([S:96][CH2:97][C:98]2[CH:103]=[CH:102][CH:101]=[C:100]([F:104])[C:99]=2[F:105])[N:81]=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:105][C:99]1[C:100]([F:104])=[CH:101][CH:102]=[CH:103][C:98]=1[CH2:97][S:96][C:82]1[N:81]=[C:80]([NH:8][S:5]([N:1]2[CH2:4][CH2:3][CH2:2]2)(=[O:7])=[O:6])[CH:85]=[C:84]([O:86][C@@H:87]([C@@H:89]2[CH2:93][O:92][C:91]([CH3:94])([CH3:95])[O:90]2)[CH3:88])[N:83]=1

Participants

9

Reactant 6

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 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]-pyrimidineHCID 86619881HCID 86619881, compound

Product 1

HCID 53628361N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4S)-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, 0.16 g), tris(dibenzylideneacetone)-dipalladium (0) (33 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (17 mg), cesium carbonate (0.28 g) and 4-chloro-2-[[(2,3-difluorophenyl)-methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine (the product of step i) (0.25 g) in dioxane (10 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 20 min. 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 column chromatography on silica gel using EtOAc/isohexane (3:7) as eluent to give the subtitle compound as a yellow oil. Yield: 0.13 g.

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 20 min
  3. extractionthe resulting mixture extracted with EtOAc
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  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-17d46ca2820a461bbe6835f29ae8aec6
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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