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【结 构 式】 
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【药物名称】 【化学名称】N-[2-[N-[5-Methoxy-1,2,3,4-tetrahydronaphthalen-2(R)-yl]-N-propylamino]ethyl]benzamide hydrochloride 【CA登记号】220772-98-5 (racemate), 220772-95-2 (racemic free base) 【 分 子 式 】C23H31ClN2O2 【 分 子 量 】402.96872 |
【开发单位】AstraZeneca (Originator) 【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Receptor Agonists, Dopamine D2 Antagonists |
合成路线1
The acylation of 5-methoxy-1,2,3,4-tetrahydronaphthalene-2-(R)-amine (I) with propionyl chloride (II) and NaOH in dichloromethane/water gives the corresponding amide (III), which is reduced with LiAlH4 in refluxing THF yielding the corresponding secondary amine (IV). The alkylation of (IV) with bromoacetonitrile (V) by means of K2CO3 in refluxing acetone affords the expected tertiary amine (VI), which is reduced with LiAlH4 in refluxing THF providing the ethylenediamine (VII). Finally, this compound is benzoylated with benzoyl chloride and NaOH in dichloromethane/water.
| 【1】 Homan, E.J.; Grol, C.J.; Unelius, L.; Wilkstrom, H.V.; Copinga, S.; Jackson, D.M.; Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT. Bioorg Med Chem 1999, 7, 7, 1263. |
| 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) | 31886 | (2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenamine; (2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenylamine | C11H15NO | 详情 | 详情 | |
| (II) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
| (III) | 31882 | N-[(2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]propanamide; N-[(2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]propanamide | C14H19NO2 | 详情 | 详情 | |
| (IV) | 14649 | (2S)-5-methoxy-N-propyl-1,2,3,4-tetrahydro-2-naphthalenamine; N-[(2S)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]-N-propylamine | C14H21NO | 详情 | 详情 | |
| (V) | 31883 | 2-bromoacetonitrile | 590-17-0 | C2H2BrN | 详情 | 详情 |
| (VI) | 31884 | 2-[[(2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl](propyl)amino]acetonitrile | C16H22N2O | 详情 | 详情 | |
| (VII) | 31885 | N(1)-[(2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]-N(1)-propyl-1,2-ethanediamine; N-(2-aminoethyl)-N-[(2R)-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]-N-propylamine | C16H26N2O | 详情 | 详情 | |
| (VIII) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |