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【结 构 式】 
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【药物名称】LY-195448 【化学名称】(R)-4-[3-[(2-Hydroxy-2-phenylethyl)amino]-3-methylbutyl]benzamide 【CA登记号】74249-21-1 (monoHCl;no stereoch.), 74249-20-0 (undefined stereoch.) 【 分 子 式 】C20H26N2O2 【 分 子 量 】326.44242 |
【开发单位】Lilly (Originator) 【药理作用】Modulators of the Therapeutic Activity of Antineoplastic Agents, Multidrug Resistance Modulators, ONCOLYTIC DRUGS |
合成路线1
The reaction of 4-(3-hydroxy-3-methylbutyl)benzoic acid (I) with HCN in acetic acid-H2SO4 gives 4-[3-(formylamino)-3-methyibutylbenzoic acid (II), which is hydrolyzed to the corresponding amine (III) with aqueous HCl at 100 C. The reaction of benzoic acid (III) with SOCl2 gives the corresponding acyl chloride (IV), which by reaction with NH3 is converted to the benzamide (V). Finally, this compound is condensed with styrene oxide (VI) by means of hexamethyldisylazane in DMSO and hydrolyzed with NaOH in butanone water.
| 【1】 Weigel, L.O. (Eli Lilly and Company); Process for preparing 2-hydroxy-2-phenethylamines. EP 0104888 . |
| 【2】 Mills, J.; Schmiegel, K.K.; Toomey, R.E. (Eli Lilly and Company); Phenethanolamines, their formulations, preparation. EP 0007206 . |
| 【3】 Castaner, J.; Prous, J.; LY-195448. Drugs Fut 1988, 13, 12, 1045. |
| 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) | 23012 | 4-(3-hydroxy-3-methylbutyl)benzoic acid | C12H16O3 | 详情 | 详情 | |
| (II) | 23013 | 4-[3-(formylamino)-3-methylbutyl]benzoic acid | C13H17NO3 | 详情 | 详情 | |
| (III) | 23014 | 4-(3-amino-3-methylbutyl)benzoic acid | C12H17NO2 | 详情 | 详情 | |
| (IV) | 23015 | 4-(3-amino-3-methylbutyl)benzoyl chloride | C12H16ClNO | 详情 | 详情 | |
| (V) | 23016 | 4-(3-amino-3-methylbutyl)benzamide | C12H18N2O | 详情 | 详情 | |
| (VI) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 详情 | 详情 |