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【结 构 式】 
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【药物名称】JNJ-17297709 【化学名称】(2R*,3aR*,12bS*)-N,N-Dimethyl-N-(3,3a,8,12b-tetrahydro-2H-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan-2-ylmethyl)amine 【CA登记号】198644-59-6 (no stereoch. at 2), 198644-93-8 (undefined isomer) 【 分 子 式 】C20H23NO 【 分 子 量 】293.41241 |
【开发单位】Janssen (Originator) 【药理作用】Anxiolytics, PSYCHOPHARMACOLOGIC DRUGS, 5-HT2A Antagonists, 5-HT2C (5-HT1C) Antagonists, Histamine H1 Antagonists |
合成路线1
Reduction of dibenzosuberenone (I) with in situ generated AlH3 affords dibenzocycloheptene (II). Subsequent epoxidation of (II) employing m-chloroperbenzoic acid gives the dibenzocycloheptaoxirane (III) (1). Epoxide ring opening in (III) with allylmagnesium bromide produces the trans alcohol (IV). Bromination of the double bond of (IV) with pyridinium tribromide leads to the trans-fused tetrahydrofuran derivative (V) as a mixture of 4 diastereoisomers. Then, substitution of the bromide ion of (V) with dimethylamine, followed by chromatographic separation of the isomers provides the target compound.
| 【1】 Alonso, J.M.; Andres, J.I.; Cid, J.M.; et al.; Synthesis of 2-aminomethyl-3,3a,8,12b-tetrahydro-2H-dibenzocyclohepta[1,2-b]furan derivatives as potential anxiolytic agents. Drugs Fut 2002, 27, Suppl. A. |
| 【2】 Gil-Lopetegui, P.; Fernandez-Gadea, F.J.; Meert, T.F. (Janssen Pharmaceutica NV); Substd. tetracyclic tetrahydrofuran derivs.. EP 0892793; JP 2000508327; WO 9738991 . |
| 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) | 29151 | 5H-dibenzo[a,d]cyclohepten-5-one; Dibenzosuberenone | 2222-33-5 | C15H10O | 详情 | 详情 |
| (II) | 58423 | 5H-dibenzo[a,d]cycloheptene | C15H12 | 详情 | 详情 | |
| (III) | 58424 | 6,10b-dihydro-1aH-dibenzo[3,4:6,7]cyclohepta[1,2-b]oxirene | C15H12O | 详情 | 详情 | |
| (IV) | 58425 | (10S,11R)-11-allyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ol | C18H18O | 详情 | 详情 | |
| (V) | 58426 | (3aR,12bS)-2-(bromomethyl)-3,3a,8,12b-tetrahydro-2H-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan | C18H17BrO | 详情 | 详情 |