反应详情

To a 20 mL vial was added 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (0.35 g, 0.87 mmol, Example 91), 6-chloropyridazine-3-sulfonyl chloride (0.20 g, 0.96 mmol, Archiv der Pharmazie and Berichte der Deutschen Pharmazeutischen Gesellschaft 1966, 229, 646), CH2Cl2 (10 mL) and triethylamine (0.61 mL, 4.4 mmol). After 24 h at room temperature, an additional 100 mg of 6-chloropyridazine-3-sulfonyl chloride was added and the solution was stirred for an additional hour. The reaction was diluted with saturated aqueous sodium bicarbonate and CH2Cl2. This was stirred for 5 min and then the solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase being collected and passed through a plug of Na2SO4. The collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes). The resulting oil was dissolved in EtOAc/heptanes, concentrated and dried under reduced pressure to afford 2-(4-(4-((6-chloropyridazin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.15 g) as a yellow solid.

1. stirringThis was stirred for 5 min
2. customthe solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase
3. custombeing collected
4. customThe collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes)
5. dissolutionThe resulting oil was dissolved in EtOAc/heptanes
6. concentrationconcentrated
7. customdried under reduced pressure