SK&F-105685

2-氮杂螺[4.5]十烷-2-丙氨酸,N,N-二甲基-8,8-二丙基- Chemical Name: N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride; 2-[3-(Dimethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane dihydrochloride
CAS No. 124796-27-6, 123018-34-8 (free base)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The hindered base,diisobutylamine,was used in the Stork enamine synthesis of valeraldehyde (I) with allyl bromide to yield the desired aldehyde (II) following acidic hydrolysis and subsequent hydrogenation.Acid-catalyzed annelation of (II) with methyl vinyl ketone provided 4,4-dipropylcyclohex-2-enone which upon hydrogenation gave (III).Piperidine-catalyzed condensation of ethyl cyanoacetate with (III) gave cyanoester (IV).Michael addition of KCN followed by acidic hydrolysis gave diacid (V).Treatment of diacid (V) with acetic anhydride gave desired anhydride (VI),which was condensed with N,N-dimethylaminopropylamine to yield the desired imide (VII).Lithium aluminum hydride reduction of the imide (VII) gave the desired diamine which was treated with anhydrous HCl/ethanol to give the required dihydrochloride salt,SK&F 105685.
📌 参考资料/链接:
参考文献标题:SK&F-105685
文献作者:Schwartz,D.A.; Badger,A.M.
参考来源:Drugs Fut 1991,16(9),815

📄 详细内容


合成路线:The synthesis of two different forms of tritiated SK&F-105685 has been described:1) The reaction of SK&F-105685 (I) with mercuric acetate and perchloric acid gives the corresponding iminium perchlorate (II),which is then reduced with NaBT4 in ethanol yielding the tritium derivative at C-1.2) The reductive tritiation of the 8-allyl-2-[3-(dimethylamino)propyl]-8-propyl-2-azaspiro[4.5]decane (III) with tritium gas over Pd/C in ethanol gives the ditritiated compound at the propyl.

参考文献标题:Synthesis of the tritium labelled azaspirane: SK&F 105685
文献作者:Landvatter,S.W.; Heys,J.R.; Senderoff,S.G.
参考来源:J Label Compd Radiopharm 1993,33(12),1113


合成路线:The hindered base,diisobutylamine,was used in the Stork enamine synthesis of valeraldehyde (I) with allyl bromide to yield the desired aldehyde (II) following acidic hydrolysis and subsequent hydrogenation.Acid-catalyzed annelation of (II) with methyl vinyl ketone provided 4,4-dipropylcyclohex-2-enone which upon hydrogenation gave (III).Piperidine-catalyzed condensation of ethyl cyanoacetate with (III) gave cyanoester (IV).Michael addition of KCN followed by acidic hydrolysis gave diacid (V).Treatment of diacid (V) with acetic anhydride gave desired anhydride (VI),which was condensed with N,N-dimethylaminopropylamine to yield the desired imide (VII).Lithium aluminum hydride reduction of the imide (VII) gave the desired diamine which was treated with anhydrous HCl/ethanol to give the required dihydrochloride salt,SK&F 105685.

参考文献标题:A study of the alkylation of enamines derived from sterically hindered amines
文献作者:Curphey,T.J.; Chu,C.C.C.; Hung,J.C.
参考来源:J Org Chem 1975,40607-14


合成路线:The hindered base,diisobutylamine,was used in the Stork enamine synthesis of valeraldehyde (I) with allyl bromide to yield the desired aldehyde (II) following acidic hydrolysis and subsequent hydrogenation.Acid-catalyzed annelation of (II) with methyl vinyl ketone provided 4,4-dipropylcyclohex-2-enone which upon hydrogenation gave (III).Piperidine-catalyzed condensation of ethyl cyanoacetate with (III) gave cyanoester (IV).Michael addition of KCN followed by acidic hydrolysis gave diacid (V).Treatment of diacid (V) with acetic anhydride gave desired anhydride (VI),which was condensed with N,N-dimethylaminopropylamine to yield the desired imide (VII).Lithium aluminum hydride reduction of the imide (VII) gave the desired diamine which was treated with anhydrous HCl/ethanol to give the required dihydrochloride salt,SK&F 105685.
参考文献标题:Acid-catalyzed annelation of alpha-alkyl aldehydes and alpha,beta-unsaturated ketones.A one-pot synthesis of 4,4-dimethyl-2-cyclohexen-1-one
文献作者:Flaugh,M.E.; Crowell,T.A.; Farlow,D.S.
参考来源:J Org Chem 1980,455399-400


产品链接: CAS No.123018-34-8››