【结 构 式】 |
【分子编号】46040 【品名】3,4-dimethyl-6,6a-dihydro-1aH-indeno[1,2-b]oxirene 【CA登记号】 |
【 分 子 式 】C11H12O 【 分 子 量 】160.21568 【元素组成】C 82.46% H 7.55% O 9.99% |
合成路线1
该中间体在本合成路线中的序号:(VI)Knoevenagel condensation of 3,4-dimethylbenzaldehyde (I) with malonic acid in the presence of piperidine afforded dimethylcinnamic acid (II), which was reduced to the saturated acid (III) by catalytic hydrogenation. Conversion of (III) to the corresponding acid chloride, followed by Friedel-Crafts cyclization, gave rise to the 1-indanone (IV). This was isomerized to the desired 2-indanone (VII) by the sequence of ketone reduction, followed by acidic dehydration of the resulting alcohol to give indene (V), which was converted to epoxide (VI) and then Lewis-acid promoted rearrangement to the 2-indanone (VII). Condensation of ketone (VII) with benzylamine and subsequent addition of trimethylsilyl cyanide to the resulting imine furnished amino nitrile (VIII). After reduction of (VIII) to the diamine (IX) with LiAlH4, the N-benzyl group was removed by transfer hydrogenolysis, yielding (X). Condensation of diamine (X) with formamidine acetate produced the target imidazoline, which was finally isolated as the fumarate salt.
【1】 Lacoste, J.-M.; Verbeuren, T.J.; Cordi, A.; Descombes, J.-J.; Couchay, C.; Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(5',6'-dimethylindane)]: A new alpha-adrenergic partial agonist. Two synthetic approaches. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-83. |
【2】 Cordi, A.; Lacoste, J.-M.; Laubie, M.; Verbeuren, T.; Descombes, J.-J. (ADIR et Cie.); Benzospiroalkene derivs., process for their preparation and pharmaceutical compsns. containing them. CA 2128359; EP 0635497; FR 2709306; JP 1995304753; US 5436261 . |
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) | 46036 | 3,4-dimethylbenzaldehyde | 5973-71-7 | C9H10O | 详情 | 详情 |
(II) | 46037 | (Z)-3-(3,4-dimethylphenyl)-2-propenoic acid | C11H12O2 | 详情 | 详情 | |
(III) | 40285 | 3-(3,4-dimethylphenyl)propionic acid | C11H14O2 | 详情 | 详情 | |
(IV) | 46038 | 5,6-dimethyl-1-indanone | C11H12O | 详情 | 详情 | |
(V) | 46039 | 5,6-dimethyl-1H-indene | C11H12 | 详情 | 详情 | |
(VI) | 46040 | 3,4-dimethyl-6,6a-dihydro-1aH-indeno[1,2-b]oxirene | C11H12O | 详情 | 详情 | |
(VII) | 46041 | 5,6-dimethyl-1,3-dihydro-2H-inden-2-one | C11H12O | 详情 | 详情 | |
(VIII) | 46042 | 2-(benzylamino)-5,6-dimethyl-2-indanecarbonitrile | C19H20N2 | 详情 | 详情 | |
(IX) | 46043 | N-[2-(aminomethyl)-5,6-dimethyl-2,3-dihydro-1H-inden-2-yl]-N-benzylamine; 2-(aminomethyl)-N-benzyl-5,6-dimethyl-2-indanamine | C19H24N2 | 详情 | 详情 | |
(X) | 46044 | 2-(aminomethyl)-5,6-dimethyl-2-indanamine; (2-amino-5,6-dimethyl-2,3-dihydro-1H-inden-2-yl)methylamine | C12H18N2 | 详情 | 详情 |