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

Temperature

100 °C

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

1. temperaturewas heated
2. temperature300 W, open vessel with cooling for 30 mins
3. customthe residue separated between DCM (150 ml) and H2O (150 ml)
4. customThe organics were separated
5. extractionthe aqueous layer was re-extracted with DCM (2×150 ml)
6. dry with materialdried (MgSO4)
7. customthe resulting residue purified by prep HPLC

ORD record

ord-6edfb587f95b4e8a8bf82a665c7f3aaa

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410123B2