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【结 构 式】 
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【药物名称】S-33004((+)-enantiomer), S-32647(racemate), S-33005 【化学名称】(-)-1-[7-(Dimethylaminomethyl)-4-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]cyclohexanol hydrochloride 【CA登记号】242473-12-7, 242473-11-6 ((+)-enantiomer), 242473-60-5 (free base), 242473-07-0 (racemate) 【 分 子 式 】C18H28ClNO2 【 分 子 量 】325.88236 |
【开发单位】Servier (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Norepinephrine Transporter (NET) Inhibitors, Serotonine Transporter (SERT) Inhibitors |
合成路线1
Lithiation of 1-cyano-5-methoxybenzocyclobutane (I), followed by addition of cyclohexanone (II), provided the 1-hydroxycyclohexyl adduct (III). The cyano group of (III) was then reduced to amine (IV) using LiAlH4. Reductive alkylation of amine (IV) with formaldehyde and NaBH3CN furnished the corresponding dimethylamino derivative, which was then converted to the corresponding hydrochloride salt with ethereal HCl.
| 【1】 Brocco, M.; Harmange, J.-C.; Peglion, J.-L.; Dessinges, A.; Newman-Tancredi, A.; Millan, M. (ADIR et Cie.); Benzocyclobutan cpds., their process for preparation and pharmaceutical compsns. containing them. CA 2264372; EP 0940386; FR 2775687; JP 1999310557; US 6107345 . |
| 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) | 51858 | 4-methoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile | C10H9NO | 详情 | 详情 | |
| (II) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (III) | 51859 | 7-(1-hydroxycyclohexyl)-4-methoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile | C16H19NO2 | 详情 | 详情 | |
| (IV) | 51860 | 1-[7-(aminomethyl)-4-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]cyclohexanol | C16H23NO2 | 详情 | 详情 |