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Osemozotan hydrochloride, MN-305, MCI-242, MKC-242

3-(1,3-苯并二氧乙醇-5-酰氧基)-n-[(2s)-2,3-二氢-1,4-苯并二恶英-2-甲基]-1-丙氨酰胺盐酸盐(1:1)Chemical Name: 2(S)-[3-(1,3-Benzodioxol-5-yloxy)propylaminomethyl]-1,4-benzodioxane hydrochloride
CAS No. 137275-80-0, 137275-81-1 (free base), 137331-63-6 (racemate), 137275-87-7 (R-isomer)
项目整合开发状态: Phase II
项目研究机构: MediciNova (Proprietary), Mitsubishi Pharma (Originator)
合成路线:Condensation of 2(R)-(tosyloxymethyl)-1,4-benzodioxane (I) with 5-(3-aminopropoxy)-1,3-benzodioxole (II) by means of triethylamine in refluxing acetonitrile,followed by salification with HCl in ethyl acetate/isopropanol.(1,2)
📌 参考资料/链接:
参考文献标题:Optically active alkylene-dioxybenzene derivs.and their use in therapy
文献作者:Iwata,H.; Baba,A.; Matsuda,T.; Egawa,M.; Tobe,A.; Saito,K.(Mitsubishi Chemical Corp.)
参考来源:EP 0446921; JP 1991264528; US 5168099; US 5234948

📄 详细内容


合成路线:Condensation of 2(R)-(tosyloxymethyl)-1,4-benzodioxane (I) with 5-(3-aminopropoxy)-1,3-benzodioxole (II) by means of triethylamine in refluxing acetonitrile,followed by salification with HCl in ethyl acetate/isopropanol.(1,2)

参考文献标题:Alkylenedioxybenzene derivs.and anxiolytic agent containing them
文献作者:Iwata,H.; Bab,A.; Matsuda,T.; Egawa,M.; Tobe,A.; Saito,K.(Institut Pasteur)
参考来源:EP 0139555; ES 8608046; JP 1985155195; US 4686281


合成路线:Condensation of 2(R)-(tosyloxymethyl)-1,4-benzodioxane (I) with 5-(3-aminopropoxy)-1,3-benzodioxole (II) by means of triethylamine in refluxing acetonitrile,followed by salification with HCl in ethyl acetate/isopropanol.(1,2)

参考文献标题:MKC-242
文献作者:Tracy,M.; Castar,J.; Prous,J.
参考来源:Drugs Fut 1997,22(3),225


合成路线:A new synthesis of MKC-242 has been described:The tosylation of 2,2-dimethyl-1,3-dioxolane-4(R)-methanol (I) with tosyl chloride in pyridine gives the expected tosylate (II),which is condensed with pyrocatechol monobenzyl ether (III) by means of NaH in N-methylpyrrolidone (NMP) yielding 4(S)-(2-benzyloxyphenoxymethyl)-2,2-dimethyl-1,3-dioxolane (IV).The hydrolysis of the dioxolane ring with hot acetic acid affords the diol (V),which is tosylated with tosyl chloride,triethylamine and dimethylaminopyridine (DMAP) in dichloromethane to give the ditosylate (VI).The debenzylation of (VI) with H2 over Pd/C in methanol/ethyl acetate yields the phenol (VII),which is cyclized by means of K2CO3 in NMP affording 2(R)-(tosyloxymethyl)-1,4-benzodioxane (VIII).Finally,this compound is condensed with 3-(1,3-benzodioxol-5-yloxy)propylamine (IX) by means of ethyl diisopropylamine in NMP.The amine (IX) used as second starting compound has been obtained as follows: The condensation of N-(3-bromopropyl)phthalimide (X) with 5-hydroxy-1,3-benzodioxole (XI) by means of NaH in hot NMP gives N-[3-(1,3-benzodioxol-5-yloxy)propyl]phthalimide (XII),which is then treated with hydrazine in refluxing methanol to obtain amine (IX).
参考文献标题:Synthesis and 5-HT1A affinity of an optically active benzodioxane derivative MKC-242; a novel anxiolytic and antidepressant agent
文献作者:Sugano,M.; Saito,K.; Yamabe,H.; Chaki,H.; Abe,M.; Tabata,R.
参考来源:214th ACS Natl Meet (Sept.7-11,Las Vegas) 1997,Abst MEDI 019


产品链接: CAS No. 137275-80-0››

产品链接: CAS No.137275-81-1››