【药物名称】SUN-9221
化学结构式(Chemical Structure):
参考文献No.547577
标题:Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity
作者:Mizuno, A.; Inomata, N.; Miya, M.; Kamei, T.; Shibata, M.; Tatsuoka, T.; Yoshida, M.; Takiguchi, C.; Miyazaki, T.
来源:Chem Pharm Bull 1999,47(2),246
合成路线图解说明:

2-Pyrrolecarboxylic acid (I) was condensed with ethyl 3-(methylamino)-propionate (II) by means of diethyl phosphorocyanidate to give amide (III). Alkaline hydrolysis of the ethyl ester group of (III) provided carboxylic acid (IV), which was cyclized in 80% polyphosphoric acid at 100 C to afford the pyrroloazepine (V). Subsequent reaction of (V) with 1,4-dichlorobutane (VI) in the presence of K2CO3 yielded the N-(4-chlorobutyl)pyrrole (VII). Treatment of (VII) with hydroxylamine hydrochloride and NaOAc furnished the E-oxime (VIII) as the major isomer. Then, displacement of the chloro atom of (VIII) with 4-(4-fluorobenzoyl)piperidine-HCl (IX) using K2CO3 and NaI yielded the title compound.

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