Sulamserod hydrochloride, RS-100302(free base), RS-100302-190

合成路线:Chlorination of 1,4-benzodioxan (I) in AcOH afforded the 6,7-dichloro derivative (II).Subsequent Friedel-Crafts acylation of (II) with acetyl chloride and AlCl3 produced ketone (III),which was nitrated employing fuming nitric acid to give nitro compound (IV).Hydrogenation of the nitro group of (IV) with concomitant hydrogenolysis of the halogen atoms in the presence of Pd/C yielded amino ketone (V).After protection of the amino group of (V) as the corresponding acetamide (VI),chlorination by means of N-chlorosuccinimide provided (VII).Optionally,amide hydrolysis with NaOH afforded amine (VIII).Aldol condensation of (VIII) with pyridine-4-carboxaldehyde (IX) in ethanolic KOH gave rise to the unsaturated ketone (X).This compound was also obtained by condensation of the N-acetylated amino ketone (VII) with aldehyde (IX) in methanolic NaOH.In a related procedure,the aldol condensation of ketone (VIII) with aldehyde (IX) using LDA in cold THF produced hydroxy ketone (XI).This was further dehydrated to unsaturated ketone (X) by means of concentrated H2SO4.Hydrogenation of the olefinic double bond of (X) over Pd/C in THF generated the saturated ketone (XII).Further hydrogenation of the pyridine ring of (XII) using Rh/Al2O3 furnished the corresponding piperidine (XIII).Alternatively,(XIII) was obtained by direct hydrogenation of (X) over Rh/Al2O3.

参考文献标题:RS-100235: A high affinity 5-HT4 receptor antagonist
文献作者:Wong,E.H.F.; Eglen,R.M.; Leung,E.; Johnson,L.G.; Langston,J.A.; Flippin,L.A.; Jahangir,A.; Bonhaus,D.W.; Clark,R.D.
参考来源:Bioorg Med Chem Lett 1995,5(18),2119


合成路线:Chlorination of 1,4-benzodioxan (I) in AcOH afforded the 6,7-dichloro derivative (II).Subsequent Friedel-Crafts acylation of (II) with acetyl chloride and AlCl3 produced ketone (III),which was nitrated employing fuming nitric acid to give nitro compound (IV).Hydrogenation of the nitro group of (IV) with concomitant hydrogenolysis of the halogen atoms in the presence of Pd/C yielded amino ketone (V).After protection of the amino group of (V) as the corresponding acetamide (VI),chlorination by means of N-chlorosuccinimide provided (VII).Optionally,amide hydrolysis with NaOH afforded amine (VIII).Aldol condensation of (VIII) with pyridine-4-carboxaldehyde (IX) in ethanolic KOH gave rise to the unsaturated ketone (X).This compound was also obtained by condensation of the N-acetylated amino ketone (VII) with aldehyde (IX) in methanolic NaOH.In a related procedure,the aldol condensation of ketone (VIII) with aldehyde (IX) using LDA in cold THF produced hydroxy ketone (XI).This was further dehydrated to unsaturated ketone (X) by means of concentrated H2SO4.Hydrogenation of the olefinic double bond of (X) over Pd/C in THF generated the saturated ketone (XII).Further hydrogenation of the pyridine ring of (XII) using Rh/Al2O3 furnished the corresponding piperidine (XIII).Alternatively,(XIII) was obtained by direct hydrogenation of (X) over Rh/Al2O3.

合成路线:Acylation of aziridine (XIV) with methanesulfonyl chloride produced sulfonamide (XV).This was then condensed with piperidine (XIII) to yield the target sulfonylaminoethyl piperidine.
参考文献标题:Process development of the synthetic route to sulamserod hydrochloride
文献作者:Kowalczyk,B.A.; et al.
参考来源:Org Process Res Dev 2001,5(2),116


产品链接: CAS No. 184159-40-8››

产品链接: CAS No.219757-90-1››