1,4-Dioxane → N-[(4aR,7aR)-6-[5-Fluoro-4-(1-hydroxy-1-methyl-ethyl)-6-methyl-pyrimidin-2-yl]-7a-isothiazol-5-yl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

Participants

Reaction Conditions

Reaction Steps

(2-Chloro-5-fluoro-6-methyl-pyrimidin-4-yl)propan-2-ol (104 mg, 0.51 mmol) is dissolved in 1,4-dioxane (3 mL). N-[(4aR,7aR)-7a-Isothiazol-5-yl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (125 mg, 0.36 mmol) is added followed by diisopropylethylamine (158 μL, 0.91 mmol). The reaction is heated via microwave irradiation in a sealed microwave vessel to 110° C. for 1 hr. The reaction is concentrated to give the crude product. The crude product is purified via HPLC using a Waters XBridge 5 μm C18 OBD 30×75 mm column and eluted with a gradient of: 36% B isocratic for 3 min followed by 36-51% B over 5 min where solvent A is 10 mM ammonium bicarbonate in water with 5% MeOH and solvent B is acetonitrile. The desired fractions are combined and diluted with saturated NaHCO3 (aq, 100 mL). The mixture is extracted with 4:1 CHCl3: isopropanol (3×100 mL). The organic layers are combined, washed with brine (1×50 mL), dried over MgSO4, filtered and concentrated to give the title compound (33 mg, 0.064 mmol): EZ/MS (m/z): 513 (M+H).

Provenance & Evidence