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【结 构 式】 
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【分子编号】29986 【品名】3-chloro-N-(3,4-dimethoxyphenethyl)-N-methyl-1-propanamine; N-(3-chloropropyl)-N-(3,4-dimethoxyphenethyl)-N-methylamine 【CA登记号】 |
【 分 子 式 】C14H22ClNO2 【 分 子 量 】271.78692 【元素组成】C 61.87% H 8.16% Cl 13.04% N 5.15% O 11.77% |
合成路线1
该中间体在本合成路线中的序号：(V)3,4-Dimethoxybenzaldehyde (I) is treated with 1,3-propanedithiol (II) to give 2-(3,4-dimethoxyphenyl)-m-dithiane (III), the oxidation product of which (IV) is reacted with N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylpropanamine chloride (V) in the presence of a base.
| 【1】 Ramuz, H.; DE 2460593 . |
| 【2】 Ramuz, H.; A new Ca2+ antagonist, Ro-111781 and its metabolites. Synthesis and physicochemical properties. Arzneim-Forsch Drug Res 1978, 28, 11, 2048. |
| 【3】 Koch, H.; Ro-11,1781. Drugs Fut 1979, 4, 2, 122. |
| 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) | 18304 | 3,4-Dimethoxybenzaldehyde; Veratraldehyde | 120-14-9 | C9H10O3 | 详情 | 详情 |
| (II) | 29729 | 1,3-propanedithiol; 3-sulfanylpropylhydrosulfide | 109-80-8 | C3H8S2 | 详情 | 详情 |
| (III) | 39515 | 2-(3,4-dimethoxyphenyl)-1,3-dithiane; 4-(1,3-dithian-2-yl)-2-methoxyphenyl methyl ether | C12H16O2S2 | 详情 | 详情 | |
| (IV) | 39516 | 2-(3,4-dimethoxyphenyl)-1lambda(6),3lambda(6)-dithiane-1,1,3,3-tetrone | C12H16O6S2 | 详情 | 详情 | |
| (V) | 29986 | 3-chloro-N-(3,4-dimethoxyphenethyl)-N-methyl-1-propanamine; N-(3-chloropropyl)-N-(3,4-dimethoxyphenethyl)-N-methylamine | C14H22ClNO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Gallopamil is obtained by condensing 2-(3,4,5-trimethoxypheny)-3-methylbutyronitrile (I) with N-(3-chloropropyl)-N-(2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine (II) in the presence of bases. Compound (I) can be prepared by reaction of 3,4,5-trimethoxyphenylacetonitrile (III) with isopropyl chloride (IV) by means of NaNH2. Compound (II) is formed from 1-bromo-3-chloropropane (V) and N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine (VI).
| 【1】 Dengel, F. (Knoll AG); Verfahren zur herstellung basisch substituerter phenylacetonitrile. DE 1154810; DE 1158083 . |
| 【2】 Mannhold, R.; Gallopamil Hydrochloride. Drugs Fut 1984, 9, 2, 108. |
| 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) | 29985 | 3-methyl-2-(3,4,5-trimethoxyphenyl)butanenitrile | C14H19NO3 | 详情 | 详情 | |
| (II) | 29986 | 3-chloro-N-(3,4-dimethoxyphenethyl)-N-methyl-1-propanamine; N-(3-chloropropyl)-N-(3,4-dimethoxyphenethyl)-N-methylamine | C14H22ClNO2 | 详情 | 详情 | |
| (III) | 29983 | 2-(3,4,5-trimethoxyphenyl)acetonitrile | 13338-63-1 | C11H13NO3 | 详情 | 详情 |
| (IV) | 29984 | 2-chloropropane | 75-29-6 | C3H7Cl | 详情 | 详情 |
| (V) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (VI) | 18938 | 2-(3,4-dimethoxyphenyl)-N-methyl-1-ethanamine; N-(3,4-dimethoxyphenethyl)-N-methylamine | 3490-06-0 | C11H17NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of 2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile (I) with N-(3-chloropropyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine (II) by means of sodium amide in refluxing toluene gives the target aminonitrile.
| 【1】 Dengel, F. (Knoll AG); Basically substd. phenyl acetonitrile cpds.. US 3261859 . |
合成路线4
该中间体在本合成路线中的序号：(IV)This compound has been obtained by two similar ways: 1) The alkylation of 4-hydroxyphenyl(2-isopropylindolizin-1-yl)sulfone (I) 1,3-dibromopropane (II) by means of K2CO3 in DMF gives 4-(3-bromopropoxy)phenyl(2-isopropylindolizin-1-yl)sulfone (III), which is finally condensed with N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine. 2) By direct condensation of sulfone (I) with the tertiary amine N-(3-chloropropyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine.
| 【1】 Gubin, J.; et al.; A novel class of calcium-entry blockers: The 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines. J Med Chem 1992, 35, 6, 981. |
| 【2】 Gubin, J.; et al.; Novel heterocyclic analogues of the new potent class of calcium entry blockers: 1-[[4-(Aminoalkoxy)phenyl]sulfonyl]indolizines. J Med Chem 1993, 36, 10, 1425. |
| 【3】 Chatelain, P.; Gubin, J.; Aminoalkoxybenzenesulfonyl heterocyclic compounds, a novel class of calcium channel antagonists. Structure-activity relationship with a focus on fantofarone, SR 33557. Drugs Fut 1993, 18, 9, 817. |
| 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) | 41267 | 4-[(2-isopropyl-1-indolizinyl)sulfonyl]phenol | C17H17NO3S | 详情 | 详情 | |
| (II) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (III) | 41268 | 4-(3-bromopropoxy)phenyl 2-isopropyl-1-indolizinyl sulfone; 1-[[4-(3-bromopropoxy)phenyl]sulfonyl]-2-isopropylindolizine | C20H22BrNO3S | 详情 | 详情 | |
| (IV) | 29986 | 3-chloro-N-(3,4-dimethoxyphenethyl)-N-methyl-1-propanamine; N-(3-chloropropyl)-N-(3,4-dimethoxyphenethyl)-N-methylamine | C14H22ClNO2 | 详情 | 详情 | |
| (V) | 18938 | 2-(3,4-dimethoxyphenyl)-N-methyl-1-ethanamine; N-(3,4-dimethoxyphenethyl)-N-methylamine | 3490-06-0 | C11H17NO2 | 详情 | 详情 |