【结 构 式】 |
【分子编号】26126 【品名】ethyl 4-(3-[3-[3-[4-(2-ethoxyphenyl)-1-piperazinyl]propoxy]-4-[(4-methylbenzyl)oxy]benzoyl]-1H-indol-1-yl)butanoate 【CA登记号】 |
【 分 子 式 】C44H51N3O6 【 分 子 量 】717.90556 【元素组成】C 73.61% H 7.16% N 5.85% O 13.37% |
合成路线1
该中间体在本合成路线中的序号:(IX)Title compound was prepared by two synthetic ways. Friedel-Crafts acylation of N-(phenylsulfonyl)indole (II) with acid chloride (I) with concomitant O-debenzylation in the presence of AlCl3 yielded ketone (III). Then, hydroxyl group alkylation of (III) with alpha-bromo-p-xylene (IV) provided p-methylbenzyl ether (V). Subsequent displacement of the chloro group in (IV) by 1-(2-ethoxyphenyl)piperazine (VI) furnished (VII). After hydrolysis of sulfonyl group of (VII) with KOH, the resulting deprotected indole (VIII) was alkylated with ethyl 4-bromobutyrate to give (IX). Finally, hydrolysis of the ethyl ester of (IX) by means of ethanolic KOH provided the title carboxylic acid potassium salt.
【1】 Sato, H.; et al.; Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5 alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives. Bioorg Med Chem Lett 1999, 9, 11, 1553. |
【2】 Yoshida, K.; Kurimoto, T.; Takei, M.; Sato, H. (Zeria Pharmaceutical Co., Ltd.); Indole deriv. and medicine containing the same. EP 0753511; US 5760040; WO 9526955 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 | |
(I) | 26120 | 4-(benzyloxy)-3-(3-chloropropoxy)benzoyl chloride | C17H16Cl2O3 | 详情 | 详情 | |
(II) | 26121 | 1-(phenylsulfonyl)-1H-indole | 40899-71-6 | C14H11NO2S | 详情 | 详情 |
(III) | 26122 | [3-(3-chloropropoxy)-4-hydroxyphenyl][1-(phenylsulfonyl)-1H-indol-3-yl]methanone | C24H20ClNO5S | 详情 | 详情 | |
(IV) | 24623 | 1-(bromomethyl)-4-methylbenzene | 104-81-4 | C8H9Br | 详情 | 详情 |
(V) | 26123 | [3-(3-chloropropoxy)-4-[(4-methylbenzyl)oxy]phenyl][1-(phenylsulfonyl)-1H-indol-3-yl]methanone | C32H28ClNO5S | 详情 | 详情 | |
(VI) | 23055 | ethyl 2-(1-piperazinyl)phenyl ether; 1-(2-ethoxyphenyl)piperazine | C12H18N2O | 详情 | 详情 | |
(VII) | 26124 | [3-[3-[4-(2-ethoxyphenyl)-1-piperazinyl]propoxy]-4-[(4-methylbenzyl)oxy]phenyl][1-(phenylsulfonyl)-1H-indol-3-yl]methanone | C44H45N3O6S | 详情 | 详情 | |
(VIII) | 26125 | [3-[3-[4-(2-ethoxyphenyl)-1-piperazinyl]propoxy]-4-[(4-methylbenzyl)oxy]phenyl](1H-indol-3-yl)methanone | C38H41N3O4 | 详情 | 详情 | |
(IX) | 26126 | ethyl 4-(3-[3-[3-[4-(2-ethoxyphenyl)-1-piperazinyl]propoxy]-4-[(4-methylbenzyl)oxy]benzoyl]-1H-indol-1-yl)butanoate | C44H51N3O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(IX)In a related procedure, dihydroxybenzoyl indole (X) was selectively alkylated at 4-hydroxyl group with alpha-bromo-p-xylene (IV) to provide ether (XI). Further alkylation of (XI) with 1-bromo-3-chloropropane gave (XII). Then, halogen displacement in (XII) by piperazine (VI) furnished the precursor ethyl ester (IX), which was finally hydrolyzed to the target carboxylic acid as above.
【1】 Sato, H.; et al.; Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5 alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives. Bioorg Med Chem Lett 1999, 9, 11, 1553. |
【2】 Yoshida, K.; Kurimoto, T.; Takei, M.; Sato, H. (Zeria Pharmaceutical Co., Ltd.); Indole deriv. and medicine containing the same. EP 0753511; US 5760040; WO 9526955 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 | |
(IV) | 24623 | 1-(bromomethyl)-4-methylbenzene | 104-81-4 | C8H9Br | 详情 | 详情 |
(VI) | 23055 | ethyl 2-(1-piperazinyl)phenyl ether; 1-(2-ethoxyphenyl)piperazine | C12H18N2O | 详情 | 详情 | |
(IX) | 26126 | ethyl 4-(3-[3-[3-[4-(2-ethoxyphenyl)-1-piperazinyl]propoxy]-4-[(4-methylbenzyl)oxy]benzoyl]-1H-indol-1-yl)butanoate | C44H51N3O6 | 详情 | 详情 | |
(X) | 26127 | ethyl 4-[3-(3,4-dihydroxybenzoyl)-1H-indol-1-yl]butanoate | C21H21NO5 | 详情 | 详情 | |
(XI) | 26128 | ethyl 4-(3-[3-hydroxy-4-[(4-methylbenzyl)oxy]benzoyl]-1H-indol-1-yl)butanoate | C29H29NO5 | 详情 | 详情 | |
(XII) | 26129 | ethyl 4-(3-[3-(3-chloropropoxy)-4-[(4-methylbenzyl)oxy]benzoyl]-1H-indol-1-yl)butanoate | C32H34ClNO5 | 详情 | 详情 |