(S)-Sotalol, Dexsotalol, (+)-Sotalol, BMY-05763-1-D(monoHCl), BMY-5763

右索他洛尔 甲烷磺酰胺,N-[4-[(1S)-1-羟基-2-[(1-甲基)氨基]乙基]苯,盐酸盐(1:1) Chemical Name: (+)-(S)-N-[4-[1-Hydroxy-2-(isopropylamino)ethyl]phenyl]methanesulfonamide; (+)-(S)-4'-[1-Hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide
CAS No. 30236-32-9, 4549-94-4 (HCl)
项目整合开发状态: Phase III
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:A chiral synthesis of d-sotalol has been reported starting from the commercially available 4'-(chloroacetyl)methanesulfonanilide (I).Enantioselective ketone reduction employing borane-tetrahydrofuran complex and (S)-2-methyloxazaborolidine (II) in tert-butyl methyl ether aforded the (S)-alcohol (III) with 96% e.e.Protection of the hydroxyl group as the triethylsilyl ether (IV) avoided formation of the undesired epoxide.Nucleophilic displacement of the chlorine of (IV) with isopropylamine to yield (V) was effected at 130 C in a pressurized steel bomb.Then,desilylation of (V) with tetrabutylammonium fluoride,followed by conversion to the hydrochloride salt furnished the title compound.In an improved procedure,chloride (III) was converted to the corresponding iodide (VI) by Finkelstein reaction with NaI in boiling acetone,followed by silylation with triethylsilyl chloride and imidazole to give (VII).Displacement of the iodine of (VII) to produce (V) was then feasible with refluxing isopropylamine at atmospheric pressure.