SNC-80

激动剂(含哌嗪基)Chemical Name: (+)-4-[(alphaR)-alpha-[(2S,5R)-4-Allyl-2,5-dimethylpiperazin-1-yl]-3-methoxybenzyl]-N,N-diethylbenzamide
CAS No. 156727-74-1
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator), National Institutes of Health (Originator)
合成路线:Friedel-Crafts acylation of toluene (II) with 3-methoxybenzoyl chloride (I) gave benzophenone (III).Subsequent methyl group oxidation using KMnO4 afforded carboxylic acid (IV),which was further converted to amide (V) by activation with SOCl2,followed by treatment with diethylamine.Reduction of the keto group of (V) by means of NaBH4 yielded alcohol (VI).The required benzhydryl chloride (VII) was then prepared by treatment of alcohol (VI) with concentrated HCl.

合成路线:The alkylation of trans-2,5-dimethylpiperazine (VIII) with allyl bromide gave rise to a racemic mixture of N-allylpiperazines,which was resolved using (-)-camphoric acid.The desired (2R,5S)-piperazine (IX) was then alkylated with benzhydryl chloride (VII) producing a mixture of the title compound and its benzhydryl epimer (X),which were separated by flash column chromatography.
📌 参考资料/链接:
参考文献标题:Probes for narcotic receptor mediated phenomena.19.Synthesis of (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80): A highly selective,nonpeptide delta opioid receptor agonist
文献作者:Calderon,S.N.; Rothman,R.B.; Porreca,F.; Flippen-Anderson,J.L.; McNutt,R.W.; Xu,H.; Smith,L.E.; Bilsky,E.J.; Davis,P.; Rice,K.C.
参考来源:J Med Chem 1994,14(37),2125

📄 详细内容


合成路线:Friedel-Crafts acylation of toluene (II) with 3-methoxybenzoyl chloride (I) gave benzophenone (III).Subsequent methyl group oxidation using KMnO4 afforded carboxylic acid (IV),which was further converted to amide (V) by activation with SOCl2,followed by treatment with diethylamine.Reduction of the keto group of (V) by means of NaBH4 yielded alcohol (VI).The required benzhydryl chloride (VII) was then prepared by treatment of alcohol (VI) with concentrated HCl.

合成路线:The alkylation of trans-2,5-dimethylpiperazine (VIII) with allyl bromide gave rise to a racemic mixture of N-allylpiperazines,which was resolved using (-)-camphoric acid.The desired (2R,5S)-piperazine (IX) was then alkylated with benzhydryl chloride (VII) producing a mixture of the title compound and its benzhydryl epimer (X),which were separated by flash column chromatography.

参考文献标题:Probes for narcotic receptor mediated phenomena: 23.Synthesis,opioid receptor binding,and bioassay of the highly selective delta agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80)
文献作者:Calderon,S.N.; Rice,K.C.; Rothman,R.B.; Porreca,F.; Flippen-Anderson,J.L.; Kayakiri,H.; Xu,H.; Becketts,K.; Smith,L.E.; Bilsky,E.J.; Davis,P.; Horvath,R.
参考来源:J Med Chem 1997,40(5),695


合成路线:In a different synthetic strategy,4-formylbenzoic acid (XI) was first coupled to diethylamine by means of EDC to yield N,N-diethyl 4-formylbenzamide (XII).The intermediate iminium salt produced by condensation between aldehyde (XII) and the chiral piperazine (IX) was then isolated as the benzotriazole adduct (XIII).Displacement of the benzotriazolyl group by the Grignard reagent (XIV) produced the title diastereoisomer as the major product,which was further enriched by recrystallization from acetonitrile/water.

参考文献标题:Report from ASCO 2002 - Docetaxel improves survival in node-positive early-stage breast cancer patients
文献作者:
参考来源:Oncology (USA) 2002,16(8),1054


合成路线:Friedel-Crafts acylation of toluene (II) with 3-methoxybenzoyl chloride (I) gave benzophenone (III).Subsequent methyl group oxidation using KMnO4 afforded carboxylic acid (IV),which was further converted to amide (V) by activation with SOCl2,followed by treatment with diethylamine.Reduction of the keto group of (V) by means of NaBH4 yielded alcohol (VI).The required benzhydryl chloride (VII) was then prepared by treatment of alcohol (VI) with concentrated HCl.

合成路线:The alkylation of trans-2,5-dimethylpiperazine (VIII) with allyl bromide gave rise to a racemic mixture of N-allylpiperazines,which was resolved using (-)-camphoric acid.The desired (2R,5S)-piperazine (IX) was then alkylated with benzhydryl chloride (VII) producing a mixture of the title compound and its benzhydryl epimer (X),which were separated by flash column chromatography.
参考文献标题:Probes of receptor mediated phenomena 19.Synthesis of (+)-4-[(alphaR)-alpha((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80): A highly selective,nonpeptide delta opioid receptor agonist
文献作者:Evans,S.M.; Lenz,G.R.
参考来源:Chemtracts - Org Chem 1994,7(6),395


产品链接: CAS No. 156727-74-1››