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【结 构 式】 
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【分子编号】24047 【品名】2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride 【CA登记号】 |
【 分 子 式 】C19H15Cl2NO3 【 分 子 量 】376.23844 【元素组成】C 60.66% H 4.02% Cl 18.85% N 3.72% O 12.76% |
合成路线1
该中间体在本合成路线中的序号：(II)This compound can be obtained by three different ways: 1) The reaction of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid (indomethacin) (I) with SOCl2 gives the corresponding acetyl chloride (II), which is treated with hydroxylamine hydrochloride and NaOH in water to afford 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetohydroxamic acid (III). Finally, this compound is hydrolyzed with 0.5 N NaOH in water. 2) The reaction of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetal-dehyde (IV) with N-hydroxybenzenesulfonamide (V) in DMSO by means of NaOH yields compound (III) already obtained. 3) By reaction of tert-butyl-5-methoxy-2-methyl-3-indolylacetate (VI) with hydroxylamine in methanol.
| 【1】 Tamietto, T.; Franzone, J.S.; De Martiis, F.; Sintesi e proprieta ntiflogistiche di alcuni acidi acetoidrossamici. Boll Chim Farm 1975, 114, 309-318. |
| 【2】 De Martiis, F.; Arrigoni-Martelli, E.; Tamietto, T.; US 3624103 . |
| 【3】 Tamietto, T.; US 4186133 . |
| 【4】 Serradell, M.N.; de Angelis, L.; Blancafort, P.; Castaner, J.; ABC-8/5. Drugs Fut 1982, 7, 6, 371. |
| 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) | 22930 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid | C19H16ClNO4 | 详情 | 详情 | |
| (II) | 24047 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride | C19H15Cl2NO3 | 详情 | 详情 | |
| (III) | 37034 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxyacetamide | C19H17ClN2O4 | 详情 | 详情 | |
| (IV) | 37035 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetaldehyde | C19H16ClNO3 | 详情 | 详情 | |
| (V) | 37036 | N-hydroxybenzenesulfonamide | 599-71-3 | C6H7NO3S | 详情 | 详情 |
| (VI) | 37038 | N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline | C16H24N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reacion of 1-(4-chlorobenzoyl)-2-methyl-5-methoxyindolyl-3-acetic acid (I) with SOCl2 in refluxing benzene gives the corresponding acyl chloride (II), which is condensed with farnesol (III) by means of triethylamine in THF.
| 【1】 Yamatsu, I.; Abe, S.; Inai, Y.; Suzuki, T.; Kinoshita, K.; Mishima, M.; Katoh, Y.; Kobayashi, S.; Murakami, M.; Yamada, K. (Eisai Co., Ltd.); Polyprenyl esters of acemethacins and anti-inflammatory method of use thereof. DE 3226687; FR 2510107; GB 2104513; JP 8315940 . |
| 【2】 Serradell, M.N.; Castaner, J.; E-0710. Drugs Fut 1984, 9, 7, 506. |
| 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) | 22930 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid | C19H16ClNO4 | 详情 | 详情 | |
| (II) | 24047 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride | C19H15Cl2NO3 | 详情 | 详情 | |
| (III) | 21965 | (2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-ol | 4602-84-0 | C15H26O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The reaction of indomethacin (I) with SOCl2 in hot benzene gives the corresponding acyl chloride (II), which is then condensed with 2,3-butanediol (III) by means of pyridine in THF.
| 【1】 Isomae, K.; Kuwamura, T.; Mogi, K.; Ogawa, Y.; Sato, S. (SSP Co., Ltd.); Esters of indomethacin. DE 3235850; GB 2125786 . |
| 【2】 Prous, J.; Castaner, J.; SY-6001. Drugs Fut 1986, 11, 3, 194. |
合成路线4
该中间体在本合成路线中的序号：(III)In a related procedure, indomethacin chloride (III) was coupled with 3-hydroxybenzaldehyde (IV) to yield ester (V). Catalytic hydrogenation of the formyl group of (V) over Pd/C produced alcohol (VI), which was further converted to chloride (VII) upon treatment with SOCl2. The chloride group of (VII) was finally displaced with silver nitrate to furnish the corresponding nitrate ester.
| 【1】 Garufi, M.; Del Soldato, P. (NicOx SA); Synthesis method of nitroxymethylphenyl esters of aspirin derivs.. WO 0044705 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 24047 | 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride | C19H15Cl2NO3 | 详情 | 详情 | |
| (IV) | 28537 | 3-hydroxybenzaldehyde | 100-83-4 | C7H6O2 | 详情 | 详情 |
| (V) | 48379 | 3-formylphenyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate | C26H20ClNO5 | 详情 | 详情 | |
| (VI) | 48380 | 3-(hydroxymethyl)phenyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate | C26H22ClNO5 | 详情 | 详情 | |
| (VII) | 48381 | 3-(chloromethyl)phenyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate | C26H21Cl2NO4 | 详情 | 详情 |