【药物名称】S-21663, PMS-812
化学结构式(Chemical Structure):
参考文献No.441117
标题:Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 1. Synthesis and biological activities of N-benzyl-N'-(arylalkyl)-2-(4', 5'-dihydro-1'H-imidazol-2'-yl)piperazines
作者:Rondu, F.; Le Bihan, G.; Wang, X.; Lamouri, A.; Touboul, E.; Dive, G.; Bellahsene, T.; Pfeiffer, B.; Renard, P.; Guardiola-Lemaitre, B.; Manechez, D.; Penicaud, L.; Ktorza, A.; Godfroid, J.J.
来源:J Med Chem 1997,40(23),3793
合成路线图解说明:

Condensation of N,N'-dibenzylethylenediamine (I) with ethyl 2,3-dibromopropionate (II) in the presence of Et3N in toluene at 80 C gave, after acidification, piperazine (III). Then, hydrogenolytic N-debenzylation in the presence of Pd/C provided ethyl piperazine-2-carboxylate (IV), which was selectively alkylated at position 4 with 1 equivalent of triphenylmethyl chloride in the presence of Et3N at -10 C to give (V). Subsequent alkylation with 2,4-dichlorobenzyl chloride (VI) in the presence of K2CO3 and a catalytic amount of KI provided (VII). Removal of the N-trityl group by treatment with HCl in either acetone or ethanol afforded piperarine (VIII), which was N-methylated by reaction with formaldehyde and formic acid in refluxing MeOH. Finally, the resulting compound (IX) was converted into the imidazoline on treatment with ethylenediamine and trimethylaluminum in refluxing toluene.

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