Methanesulfonyl chloride → 2-Phenoxyethyl methanesulfonate

Synthesis of N-[1-(2-phenoxyethan-1-yl)piperidin-4-ylmethyl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide Under nitrogen gas, 0.37 ml (4.78 mM) of methanesulfonyl chloride was added to a solution of 0.44 g (3.18 mM) of phenoxyethanol and 0.89 ml (6.39 mM) of triethylamine in methylene chloride (6 ml) at 0° C. and the mixture was stirred at the prevailing temperature for 35 minutes. The reaction was stopped by adding saturated aqueous solution of sodium hydrogen carbonate and the reaction mixture was extracted with diethyl ether. The organic layer was washed serially with water and saturated aqueous solution of sodium chloride and dried over MgSO4. The solvent was then distilled off under reduced pressure to provide 0.6989 g (<3.18 mM) of phenoxyethyl mesylate. To a solution of 0.58 g (1.5 mM) of N-(piperidin-4-ylmethyl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride and 1.0 ml (7.2 mM) of triethylamine in ethanol (6.0 ml) was added 0.6989 g (<3.18 mM) of the above phenoxyethyl mesylate at room temperature and the mixture was refluxed under nitrogen for 17 hours. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with chloroform. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4. The resulting crude product was purified by column chromatography (methanol/ethyl acetate 30-40%) to provide the title compound.

1. extractionthe reaction mixture was extracted with diethyl ether
2. washThe organic layer was washed serially with water and saturated aqueous solution of sodium chloride
3. dry with materialdried over MgSO4
4. distillationThe solvent was then distilled off under reduced pressure

ORD-Eintrag

ord-de88489cfd4c4fd1bd0161b5b5129c76

Quelldatensatz

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06235731B1