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

HRID 1024908Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024908
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[CH:6]1(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:47]1[CH:52]=[C:51]([O:53][CH:54]2COC(C3C=CC=CC=3)O[CH2:55]2)[N:50]=[C:49]([S:66][CH2:67][C:68]2[CH:73]=[CH:72][CH:71]=[C:70]([F:74])[C:69]=2[F:75])[N:48]=1.[O:76]1[CH2:81][CH2:80][O:79][CH2:78][CH2:77]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:75][C:69]1[C:70]([F:74])=[CH:71][CH:72]=[CH:73][C:68]=1[CH2:67][S:66][C:49]1[N:48]=[C:47]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:52]=[C:51]([O:53][C@@H:54]([C@H:81]2[CH2:80][O:79][C:78]([CH3:77])([CH3:6])[O:76]2)[CH3:55])[N:50]=1

Komponenten

7

Edukt 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 72879MethanesulfonamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 536283394-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine

Produkt 1

HCID 67051274N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy)-4-pyrimidinyl]-methanesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Versuchsvorschrift

A mixture of methanesulfonamide (0.11 g), tris(dibenzylideneacetone)dipalladium (0) (26 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (14 mg), cesium carbonate (0.14 g) and 4-chloro-2-[[(2,3-difluorophenyl)-methyl]thio]-6-[(2-phenyl-1,3-dioxan-5-yl)oxy]-pyrimidine (the subtitle product of example 46 step v) (0.12 g) in dioxane (6 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 15 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: 0.12 g.

Quellen und Nachweise

ORD-Eintrag
ord-80a8e28d4710422eac96d9fe6382d971
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722883B2

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