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 1024906Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024906
[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

Komponenten

8

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-6e7f083df65e4e55abe8b22f68908dd0
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722883B2

Notizen zur Reaktion

Wird geladen…