Rotigotine hydrochloride, SPM-962(patch), (-)-N-0437, N-0437(undefined isomer), N-0923, Neupro, Rotigotine CDS
盐酸罗替戈汀 (R)-6-(丙基(2-(噻吩-2-基)乙基)氨基)-5,6,7,8-四氢萘-1-醇盐酸盐 (R)-6-(丙基(2-(噻吩-2-基)乙基)氨基)-5,6,7,8-四氢萘-1-醇Chemical Name: (-)-(S)-2-[N-Propyl-N-[2-(2-thienyl)ethyl]amino]-5-hydroxy-1,2,3,4-tetrahydronaphthalene hydrochloride; (-)-(S)-6-[N-Propyl-N-[2-(2-thienyl)ethyl]amino]-5,6,7,8-tetrahydro-1-naphthalenol hydrochloride
CAS No. 125572-93-2, 125572-92-1 ((R)-isomer), 112835-48-0 ((R)-isomer, free base), 99755-59-6 (free base), 113349-24-9 (racemic, free base), 102120-99-0 (undefined isomer), 92206-54-7 (undefined isomer, free base)
项目整合开发状态: Pre-Registered
项目研究机构: Aderis (Originator), Mitsubishi Pharma (Licensee), Otsuka (Licensee), Schwarz (Licensee)
合成路线:The overall synthetic approach to N-0923 is described:Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II),which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol.Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV),from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt.Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI),which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII).Treatment with anhydrous hydrogen chloride in ether provides N-0923.
📌 参考资料/链接：
参考文献标题:Resolution of racemic mixtures
文献作者:Manimaran,T.; Impastato,F.J.(Ethyl Corporation)
参考来源:US 4968837
📄 详细内容
合成路线:The overall synthetic approach to N-0923 is described:Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II),which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol.Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV),from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt.Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI),which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII).Treatment with anhydrous hydrogen chloride in ether provides N-0923.
参考文献标题:N-0923
文献作者:Cusack,N.J.; Peck,J.V.
参考来源:Drugs Fut 1993,18(11),1005
合成路线:The overall synthetic approach to N-0923 is described:Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II),which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol.Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV),from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt.Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI),which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII).Treatment with anhydrous hydrogen chloride in ether provides N-0923.
参考文献标题:Synthesis of alkoxy-1,2,3,4-tetrahydronaphthalene derivatives
文献作者:Evans,D.; Grey,T.F.; Richards,K.E.; Ames,D.E.; Islip,P.J.
参考来源:J Chem Soc 1965,2636-41
合成路线:The overall synthetic approach to N-0923 is described:Methylation of 1,6-dihydroxynaphthalene (I) with dimethyl sulfate provides 1,6-dimethoxynaphthalene (II),which is converted to 5-methoxy-2-tetralone (III) by reduction with sodium in ethanol.Reductive amination of (III) with propylamine results in the racemic 5-methoxy-2-N-propylaminotetralin (IV),from which the (-)-enantiomer (V) is obtained by fractional crystallization of the dibenzoyl-L-tartaric acid (L-DBTA) salt.Demethylation with aqueous hydrobromic acid affords (-)-(S)-5-hydroxy-2-N-propylaminotetralin (VI),which is reductively alkylated with thienylacetic acid in the presence of trimethylaminoborane to (-)-(S)-5-hydroxy-2-[N-propyl-N-[2-(2-thienyl)ethyl]amino]tetralin (VII).Treatment with anhydrous hydrogen chloride in ether provides N-0923.
参考文献标题:Ten Hoeve,W.,Wynberg,H.The design of resolving agents.Chiral phosphoric acids
文献作者:Wynberg,H.; Ten Hoeve,W.
参考来源:J Org Chem 1985,504508-14