【结 构 式】 |
【药物名称】 【化学名称】1-Ethyl-7-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione 4-oxime 【CA登记号】150159-63-0 【 分 子 式 】C23H30FN5O2 【 分 子 量 】427.52625 |
【开发单位】Daiichi Suntory Pharma (Originator) 【药理作用】Antiplatelet Therapy, CARDIOVASCULAR DRUGS, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Hypertension, Treatment of, 5-HT2 Antagonists, alpha1-Adrenoceptor Antagonists |
合成路线1
Treatment of methyl pyrrole-2-carboxylate (I) with KOtBu and 18-crown-6 in Et2O, followed by reaction with ethyl iodide (II) in Et2O, yields methyl 1-ethylpyrrole-2-carboxylate (III), which is then subjected to saponification with NaOH to afford carboxylic acid (IV). Condensation of (IV) with beta-alanine benzyl ester p-toluene sulfonate (V) in the presence of diethyl phosphorocyanidate (DEPC) and Et3N in DMF provides benzyl ester (VI), which is then hydrogenated over Pd/C in THF, furnishing carboxylic acid (VII). Cyclization of (VII) with polyphosphoric acid (PPA) affords derivative (VIII), which is then treated with NaH in DMF and alkylated with chloro derivative (IX) in DMF to produce compound (X). Finally, treatment of (X) with hydroxylamine hydrochloride and NaOAc affords the target compound.
【1】 Mizuno, A.; Miya, M.; Inomata, N.; Tatsuoka, T.; Ishihara, T. (Suntory Ltd.); Pyrroloazepine cpd.. EP 0557526; JP 1993503481; US 5399557; WO 9303032 . |
【2】 Yamaki, A.; Tatsuoka, T.; Miya, M.; Nakanishi, K.; Mizuno, A.; Takiguchi, C.; Hidaka, T.; Kamei, T.; Shibata, M.; Inomata, N.; Studies on antihypertensive agents with antithrombotic activity. 2. Syntheses and pharmacological evaluation of pyrrolo[2,3-c]azepine derivatives. Chem Pharm Bull 2000, 48, 8, 1129. |
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) | 45616 | methyl 1H-pyrrole-2-carboxylate | C6H7NO2 | 详情 | 详情 | |
(II) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
(III) | 45617 | methyl 1-ethyl-1H-pyrrole-2-carboxylate | C8H11NO2 | 详情 | 详情 | |
(IV) | 45618 | 1-ethyl-1H-pyrrole-2-carboxylic acid | C7H9NO2 | 详情 | 详情 | |
(V) | 30194 | benzyl 3-aminopropanoate | 27019-47-2 | C10H13NO2 | 详情 | 详情 |
(VI) | 45619 | benzyl 3-[[(1-ethyl-1H-pyrrol-2-yl)carbonyl]amino]propanoate | C17H20N2O3 | 详情 | 详情 | |
(VII) | 45620 | N-[(1-ethyl-1H-pyrrol-2-yl)carbonyl]-beta-alanine | C10H14N2O3 | 详情 | 详情 | |
(VIII) | 45621 | 1-ethyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione | C10H12N2O2 | 详情 | 详情 | |
(IX) | 45622 | 1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine | C13H18ClFN2 | 详情 | 详情 | |
(X) | 45623 | 1-ethyl-7-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione | C23H29FN4O2 | 详情 | 详情 |