OPC-33509

Chemical Name: (-)-(R,R)-N-Cyclopropyl-N-(2-hydroxycyclohexyl)-N'-[3-(2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]urea
项目整合开发状态: Preclinical
项目研究机构: Otsuka (Originator)
合成路线:OP C-33509 has been obtained by coupling imidazolecarboxamide (VI) with amine (IX) in refluxing CHCl3.The intermediates (VI) and (IX) have been obtained as follows:1) Alkylation of 6-hydroxycarbostyril (I) with N-(3-bromopropyl)- phthalimide (II) in the presence of K2CO3 in DMF furnished the phthalimidopropyl ether (III).Subsequent hydrazinolysis of the phthalimide in refluxing EtOH provided the primary amine (IV).Then,the imidazolecarboxamide (VI) was obtained by treating amine (IV) with 1,1'-carbonyldiimidazole (V) and two equivalents of imidazole in DMSO.2) Ring opening of 1,2 epoxycyclohexane (VII) with cyclopropylamine (VIII) gave the racemic trans aminoalcohol.Resolution of enantiomers (IX) and (X) was accomplished by esterification with (S)-mandelic acid (XI),followed by chromatographic separation of the diastereomeric esters.Hydrolysis of the desired ester (XII) then provided optically pure aminoalcohol (IX).Finally,the target urea derivative was obtained by coupling imidazolyl urea (VI) with amine (IX) in refluxing chloroform.