ReN-1869, NNC-05-1869
1-[3-(10,11-二氢-5H-二苯并[a,d]环庚烯-5-亚基)丙基]哌啶-3(R)-羧酸 (3R)-1-[3-(5,6-二氢二苯并[1,2-a:1//',2//'-e][7]烯基-11-伊酮)丙基]哌啶-3-羧酸盐酸盐 Chemical Name: 1-[3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]piperidine-3(R)-carboxylic acid
CAS No. 170149-99-2, 170149-76-5 (HCl)
项目整合开发状态: Phase II
项目研究机构: Novo Nordisk (Originator), ReNeuron (Licensee)
合成路线:Addition of cyclopropylmagnesium bromide (II) to dibenzocycloheptanone (I) afforded the carbinol adduct (III),which was further rearranged to the bromopropylidene derivative (IV) upon treatment with bromotrimethylsilane.Alkylation of ethyl (R)-nipecotate (V) with bromide (IV) gave the tertiary amine (VI).The ethyl ester group of (VI) was finally hydrolyzed under basic conditions to furnish the corresponding carboxylic acid.
📌 参考资料/链接：
参考文献标题:Novel heterocyclic cpds.
文献作者:Andersen,K.E.; Olsen,U.B.; Petersen,H.; Gr鴑vald,F.C.; Sonnewald,U.; J鴕gensen,T.K.; Andersen,H.S.(Novo Nordisk A/S)
参考来源:US 5595989; US 5668129; US 5688788; US 5693649; US 5712292; US 5721254; US 5795888; US 6043239; WO 9518793
📄 详细内容
合成路线:Addition of cyclopropylmagnesium bromide (II) to dibenzocycloheptanone (I) afforded the carbinol adduct (III),which was further rearranged to the bromopropylidene derivative (IV) upon treatment with bromotrimethylsilane.Alkylation of ethyl (R)-nipecotate (V) with bromide (IV) gave the tertiary amine (VI).The ethyl ester group of (VI) was finally hydrolyzed under basic conditions to furnish the corresponding carboxylic acid.
参考文献标题:Novel method
文献作者:Olsen,U.B.(Novo Nordisk A/S)
参考来源:JP 1999507947; WO 9722338
合成路线:The condensation of dibenzocycloheptylidene derivative (I) with radiolabelled piperidine-3-carboxylic acid ethyl ester (II) by means of K2CO3 in ethyl acetate gives the adduct (III),which is hydrolyzed with aqueous HCl to yield the carboxylic acid (IV).Finally,this compound is submitted to optical resolution by means of chiral chromatography to provide the chiral radiolabelled compound.
合成路线:The reduction of 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid (I) with tritium over PdO in methanol gives the racemic ditritiated compound (II),which is then submitted to optical resolution by chiral chromatography to afford the chiral radiolabelled compound.
参考文献标题:Radiolabelling of NNC 05-1869,a compound for treatment of diabetic neuropathy
文献作者:Valsborg,J.S.; Foged,C.
参考来源:J Label Compd Radiopharm 2002,45(4),351
产品链接: CAS No. 170149-99-2›› 产品链接: CAS No.170149-76-5››