【结 构 式】 |
【分子编号】31798 【品名】N-methyl-N-(1H-pyrrol-2-ylcarbonyl)-beta-alanine 【CA登记号】 |
【 分 子 式 】C9H12N2O3 【 分 子 量 】196.20596 【元素组成】C 55.09% H 6.16% N 14.28% O 24.46% |
合成路线1
该中间体在本合成路线中的序号:(IV)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 |