Chemical Name: (E)-3-Chloro-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylbenzo[b]thiophene-7-methanamine hydrochloride
CAS No. 87906-33-0, 87906-31-8 (free base), 87906-32-9 (Z-isomer, free base)
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:A new synthesis of SDZ-87469 has been published:The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II),which is selectively dechlorinated with butyllithium and hydrolysis,yielding 3-chloro-7-methylbenzo[b]thiophene (III).The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV),which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF.The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol.Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.
📄 详细内容
合成路线:A new synthesis of SDZ-87469 has been published:The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II),which is selectively dechlorinated with butyllithium and hydrolysis,yielding 3-chloro-7-methylbenzo[b]thiophene (III).The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV),which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF.The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol.Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.
参考文献标题:Synthesis and structure-activity relationships of benzo[b]thienylallylamine antimycotics
文献作者:Nussbaumer,P.; Petranyi,G.; Stz,A.
参考来源:J Med Chem 1991,34(1),65-73
合成路线:A new synthesis of SDZ-87469 has been published:The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II),which is selectively dechlorinated with butyllithium and hydrolysis,yielding 3-chloro-7-methylbenzo[b]thiophene (III).The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV),which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF.The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol.Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.
参考文献标题:
文献作者:Petranyi,G.; Stz,A.
参考来源:J Med Chem 1984,27(12),1539-43
合成路线:A new synthesis of SDZ-87469 has been published:The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II),which is selectively dechlorinated with butyllithium and hydrolysis,yielding 3-chloro-7-methylbenzo[b]thiophene (III).The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV),which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF.The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol.Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.
参考文献标题:
文献作者:Loozen,H.; Godefroi,E.
参考来源:J Org Chem 1973,38(5),1056-7
合成路线:A new synthesis of SDZ-87469 has been published:The chlorination of 7-methylbenzo[b]thiophene (I) gives 2,3-dichloro-7-methylbenzo[b]thiophene (II),which is selectively dechlorinated with butyllithium and hydrolysis,yielding 3-chloro-7-methylbenzo[b]thiophene (III).The bromination of (III) with N-bromosuccinimide (NBS) in DMF affords 7-(bromomethyl)-3-chlorobenzo[b]thiophene (IV),which is finally condensed with N,6,6-trimethylhep-2-en-4-yn-1-amine (V) (E + Z mixture) by means of K2CO3 in DMF.The pure E-isomer is obtained by crystallization of the E + Z mixture of the hydrochlorides in ethanol.Amine (V) is obtained by reaction of the corresponding bromo derivative (IV) with methylamine.
参考文献标题:
文献作者:Stz,A.; Nussbaumer,P.
参考来源:Rev Iberoam Micol 1988,5(1),89