【结 构 式】 |
【分子编号】36198 【品名】N-(3,5-dimethoxyphenethyl)-N-methylamine; 2-(3,5-dimethoxyphenyl)-N-methyl-1-ethanamine 【CA登记号】 |
【 分 子 式 】C11H17NO2 【 分 子 量 】195.26152 【元素组成】C 67.66% H 8.78% N 7.17% O 16.39% |
合成路线1
该中间体在本合成路线中的序号:(III)This compound can be prepared by two related ways: 1) The reaction of (3,5-dimethoxyphenyl)ethylamine (I) with ethyl chlorocarbonate (A) in CH2Cl2 gives ethyl N-[2-(3,5-dimethoxyphenyl)ethyl]carbamate (II), which is reduced with sodium dihydro-bis(2-methoxyethyl)aluminate in THF yielding N-methyl-(3,5-dimethoxyphenyl)ethylamine (III). Partial hydrogenation of (III) with Li in dry NH3 affords N-methyl-1,5-dimethoxycyclohexa-1,4-diene-3-ethylamine (IV), which is hydrolyzed with refluxing aqueous acetic acid giving 3-[2-(methylamino)ethyl]cyclohexane-1,5-dione (V). The cyclocondensation of (V) with 2-amino-3-pentanone (VI) [prepared by reduction with Zn of 2-isonitroso-3-pentanone (VII)] in refluxing acetic acid yields 6-[2-(N-methylamino)ethyl]-2-methyl-3-ethyl-6,7-dihydro-(5H)-4(1H,5H)indolone (VIII). Finally, this compound is cyclized again with formaldehyde in refluxing octanol. 2) The cyclization of (III) with formaldehyde as before gives 3,4-dihydro-1H-6,8-dimethoxy-2-methylisoquinoline (IX), which is reduced partially with Li in dry NH3 as before yielding 1,2,3,4,4a,7-hexahydro-6,8-dimethoxy-2-methylisoquinoline (X). The hydrolysis of (X) with refluxing acetic acid affords octahydro-2-methylisoquinolin-6,8-dione (XI), which is then cyclized with (VI) as before. The racemic base is resolved by treatment with d-(+)-tartaric acid in methanol and a fractional crystallization.
【1】 Cheung, H.-C.; Todaro, L.; Morgan, K.D.; Blount, J.F.; n, G.L.; Boff, E.; Berger, L.; Davidson, A.B.; A dopamine receprtor model and its application in the design of a new class of igid pyrrolo[2,3-g]isoquinoline anti-psychotics. J Med Chem 1981, 24, 9, 1026-34. |
【2】 Berger, L.; Olson, G.L. (F. Hoffmann-La Roche AG); Isoquinoline derivs., process for their preparation, intermediates and pharmaceutical compsns. containing them. EP 0010661 . |
【3】 Serradell, M.N.; Blancafort, P.; Owen, R.T.; Castaner, J.; RO-22-1319. Drugs Fut 1983, 8, 10, 869. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
(I) | 36206 | 3,5-dimethoxyphenethylamine; 2-(3,5-dimethoxyphenyl)-1-ethanamine | 3213-28-3 | C10H15NO2 | 详情 | 详情 |
(II) | 36197 | ethyl 3,5-dimethoxyphenethylcarbamate | C13H19NO4 | 详情 | 详情 | |
(III) | 36198 | N-(3,5-dimethoxyphenethyl)-N-methylamine; 2-(3,5-dimethoxyphenyl)-N-methyl-1-ethanamine | C11H17NO2 | 详情 | 详情 | |
(IV) | 36199 | 2-(3,5-dimethoxy-2,5-cyclohexadien-1-yl)-N-methyl-1-ethanamine; N-[2-(3,5-dimethoxy-2,5-cyclohexadien-1-yl)ethyl]-N-methylamine | C11H19NO2 | 详情 | 详情 | |
(V) | 36200 | 5-[2-(methylamino)ethyl]-1,3-cyclohexanedione | C9H15NO2 | 详情 | 详情 | |
(VI) | 36203 | 2-amino-3-pentanone | C5H11NO | 详情 | 详情 | |
(VII) | 36202 | 2,3-pentanedione 2-oxime | C5H9NO2 | 详情 | 详情 | |
(VIII) | 36201 | 3-ethyl-2-methyl-6-[2-(methylamino)ethyl]-1,5,6,7-tetrahydro-4H-indol-4-one | C14H22N2O | 详情 | 详情 | |
(IX) | 36207 | 6,8-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline; 6-methoxy-2-methyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether | C12H17NO2 | 详情 | 详情 | |
(X) | 36204 | 6,8-dimethoxy-2-methyl-1,2,3,4,4a,7-hexahydroisoquinoline; 6-methoxy-2-methyl-1,2,3,4,4a,7-hexahydro-8-isoquinolinyl methyl ether | C12H19NO2 | 详情 | 详情 | |
(XI) | 36205 | 2-methylhexahydro-6,8(2H,7H)-isoquinolinedione | C10H15NO2 | 详情 | 详情 |