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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 2388788
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2388788
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].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:47]1[CH:52]=[C:51]([O:53][C@@H:54]([C@H:56]2[CH2:60][O:59][C:58]([CH3:62])([CH3:61])[O:57]2)[CH3:55])[N:50]=[C:49]([S:63][CH2:64][C:65]2[CH:70]=[CH:69][CH:68]=[C:67]([F:71])[C:66]=2[F:72])[N:48]=1>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:72][C:66]1[C:67]([F:71])=[CH:68][CH:69]=[CH:70][C:65]=1[CH2:64][S:63][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:56]2[CH2:60][O:59][C:58]([CH3:61])([CH3:62])[O:57]2)[CH3:55])[N:50]=1
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Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866198804-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

Produkt 1

HCID 67051274
N-[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 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

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-[(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy]-pyrimidine (the subtitle product of example 45 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.

Quellen und Nachweise

ORD-Eintrag
ord-965efa15178445ea8f0dcd132a8fcfbf
Quelldatensatz
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08269002B2

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