Cesium carbonate → N-(2-[(2,3-Difluorobenzyl)thio]-6-{[(1R,2R)-2-hydroxy-methylpropyl]oxy}pyrimidin-4-yl)-(3R,5S)-3,5-dimethylpiperazine-1-sulfonamide

온도

100 °C

To a solution of (2R,6S)-2,6-Dimethylpiperazine (1 g) in dioxane (10 ml) was added sulfamide (0.746 g) and the reaction mixture was then heated at reflux in dioxane for 3d. The reaction mixture was partitioned between EtOAc (150 ml) and H2O (150 ml) and the aqueous re-extracted with EtOAc (2×150 ml). Organics were collected dried and reduced in vacuo to yield (3R,5S)-3,5-dimethylpiperazine-1-sulfonamide as a white solid (1.05 g). A mixture of (3R,5S)-3,5-dimethylpiperazine-1-sulfonamide (0.541 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.731 g) and (2R,3R)-3-({6-chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)butan-2-ol ((the product of example 4 step i), 0.541 g) in dioxane (40 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 20 min. The reaction mixture was then reduced in vacuo and the residue separated between DCM (200 ml) and H2O (200 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×200 ml). Organics were combined, dried (MgSO4) and reduced in vacuo and the resulting residue was purified by prep HPLC to give the title compound as a white solid. Yield: 80 mg

1. temperaturewas heated
2. temperature300 W, open vessel with cooling for 20 min
3. customthe residue separated between DCM (200 ml) and H2O (200 ml)
4. customThe organics were separated
5. extractionthe aqueous layer was re-extracted with DCM (2×200 ml)
6. dry with materialdried (MgSO4)
7. customthe resulting residue was purified by prep HPLC

ORD 기록

ord-c273943a8db44085a6085c17108789b6

출처 데이터셋

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08722883B2