Reaktion #2046231

Reaktionsgleichung

azetidine-1-sulfonamide

2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl

cesium carbonate

2-({6-chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)ethanol

→

title compound

N-[2-[(2,3-Difluorobenzyl)thio]-6-(2-hydroxyethoxy)pyrimidin-4-yl]-azetidine-1-sulfonamide

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperatur300 W, open vessel with cooling for 30 mins
3. 3
   Sonstigethe residue separated between DCM (150 ml) and H2O (150 ml)
4. 4
   SonstigeThe organics were separated
5. 5
   Extraktionthe aqueous layer was re-extracted with DCM (2×150 ml)
6. 6
   Trocknendried (MgSO4)
7. 7
   Sonstigethe resulting residue purified by prep HPLC

Vorschrift

A mixture of azetidine-1-sulfonamide (0.33 g, prepared according to patent WO2004/011443), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.585 g) and 2-({6-chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)ethanol ((the product from example 112 step ii), 0.400 g) in dioxane (20 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 30 mins. The reaction mixture was then reduced in vacuo and the residue separated between DCM (150 ml) and H2O (150 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×150 ml). Organics were combined, dried (MgSO4) and reduced in vacuo and the resulting residue purified by prep HPLC to give the title compound as a white solid. Yield: 0.13 g

Quelle