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【结 构 式】 
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【药物名称】 【化学名称】N,N'-(1,3-Propylene)bis(oxy)bis(naphthalen-7,1-diyl)bis(1,2-ethylene)bis(acetamide) 【CA登记号】296280-56-3 【 分 子 式 】C31H34N2O4 【 分 子 量 】498.62763 |
【开发单位】Servier (Originator) 【药理作用】PHARMACOLOGICAL TOOLS, Melatonin MT1 Antagonists |
合成路线1
Demethylation of N-[2-(7-methoxynaphth-1-yl)ethyl]acetamide (I) with boron tribromide-dimethyl sulfide complex affords phenol (II). This is then alkylated with 3-bromopropanol (III) in the presence of K2CO3 to provide the hydroxypropyl derivative (IV). After conversion of alcohol (IV) into the corresponding mesylate (V), condensation with a further equivalent of phenol (II) in hot DMF furnishes the target dimeric compound
| 【1】 Guillaumet, G.; Renard, P.; Lesieur, D.; Yous, S.; Descamps-Francois, C.; Lefoulon, F.; Viaud, M.-C.; Delagrange, P.; Bennejean, C. (ADIR et Cie.); Substd. dimeric cpds., process for their preparation and pharmaceutical compsns. thereof. EP 1038863; FR 2791344; JP 2000319242; US 2002035114; US 6319930; US 6635650 . |
| 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) | 63525 | N-{2-[7-(methyloxy)-1-naphthalenyl]ethyl}acetamide | C15H17NO2 | 详情 | 详情 | |
| (II) | 63526 | N-[2-(7-hydroxy-1-naphthalenyl)ethyl]acetamide | C14H15NO2 | 详情 | 详情 | |
| (III) | 12573 | 3-Bromo-1-propanol; 3-Bromopropanol | 627-18-9 | C3H7BrO | 详情 | 详情 |
| (IV) | 63527 | N-(2-{7-[(3-hydroxypropyl)oxy]-1-naphthalenyl}ethyl)acetamide | C17H21NO3 | 详情 | 详情 | |
| (V) | 63528 | 3-({8-[2-(acetylamino)ethyl]-2-naphthalenyl}oxy)propyl methanesulfonate | C18H23NO5S | 详情 | 详情 |
合成路线2
In an alternative method, the title dimer compound is obtained by condensation of two equivalents of N-[2-(7-hydroxynaphth-1-yl)ethyl]acetamide (I) with 1,3-dibromopropane (II) in the presence of K2CO3 in acetonitrile
| 【1】 Descamps-François, C.; Yous, S.; Chavatte, P.; Audinot, V.; Bonnaud, A.; Boutin, J.A.; Delagrange, P.; Bennejean, C.; Renard, P.; Lesieur, D.; Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands. J Med Chem 2003, 46, 7, 1127. |