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【结 构 式】 
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【药物名称】SUN-9221 【化学名称】1-[4-[4-(4-Fluorobenzoyl)piperidin-1-yl]butyl]-4(E)-(hydroxyimino)-7-methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one 【CA登记号】136976-16-4 【 分 子 式 】C25H31FN4O3 【 分 子 量 】454.54922 |
【开发单位】Daiichi Suntory Pharma (Originator) 【药理作用】Antiplatelet Therapy, CARDIOVASCULAR DRUGS, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Hypertension, Treatment of, alpha1-Adrenoceptor Antagonists |
合成路线1
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.
| 【1】 Miya, M.; Miyazaki, T.; Inomata, N.; Tatsuoka, T.; Mizuno, A.; Kamei, T.; Takiguchi, C.; Yoshida, M.; Shibata, M.; Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity. Chem Pharm Bull 1999, 47, 2, 246. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 31796 | Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid | 634-97-9 | C5H5NO2 | 详情 | 详情 |
| (II) | 20771 | ethyl 3-(methylamino)propanoate | C6H13NO2 | 详情 | 详情 | |
| (III) | 31797 | ethyl 3-[methyl(1H-pyrrol-2-ylcarbonyl)amino]propanoate | C11H16N2O3 | 详情 | 详情 | |
| (IV) | 31798 | N-methyl-N-(1H-pyrrol-2-ylcarbonyl)-beta-alanine | C9H12N2O3 | 详情 | 详情 | |
| (V) | 31799 | 7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione | C9H10N2O2 | 详情 | 详情 | |
| (VI) | 31800 | 1,4-dichlorobutane | 110-56-5 | C4H8Cl2 | 详情 | 详情 |
| (VII) | 31801 | 1-(4-chlorobutyl)-7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione | C13H17ClN2O2 | 详情 | 详情 | |
| (VIII) | 31802 | 1-(4-chlorobutyl)-7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione 4-oxime | C13H18ClN3O2 | 详情 | 详情 | |
| (IX) | 21497 | (4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine | 56346-57-7 | C12H14FNO | 详情 | 详情 |