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【结 构 式】 
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【分子编号】48701 【品名】1-(p-Methoxyphenyl)ethylamine; 1-Amino-2-(4-methoxyphenyl)ethane; 2-(4-Methoxyphenyl)ethylamine; 4-(2-Aminoethyl)anisole; 4-Methoxybenzeneethanamine; 4-Methoxyphenethylamine; 4-Methoxyphenylethylamine; p-Methoxy phenethylamine; p-Methoxy phenylethylamine 【CA登记号】55-81-2 |
【 分 子 式 】C9H13NO 【 分 子 量 】151.20836 【元素组成】C 71.49% H 8.67% N 9.26% O 10.58% |
合成路线1
该中间体在本合成路线中的序号：(I)Condensation of 2-(4-methoxyphenyl)ethylamine (I) with either 5-chloro-2-methoxybenzoic acid (II) by means of CDI and TEA or 5-chloro-2-methoxybenzoyl chloride (III) by means of pyridine and DMAP gives the corresponding benzamide (IV), which by treatment with chlorosulfonic acid yields the sulfonyl chloride (V). Reaction of compound (V) with aqueous ammonia in acetone affords the expected sulfonamide (VI), which is finally treated with methyl isothiocyanate (VII) by means of either KOtBu or NaH in DMF.
| 【3】 Englert, H.; Mania, D.; Hartung, J.; Gögelein, H.; Kaiser, J.; Linz, W.; Wettlaufer, D. (Aventis Pharma Deutschland GmbH); Substd. benzenesulfonylureas and -thioureas, process for their preparation and their use as pharmaceuticals. CA 2116165; EP 0612724; JP 1995304728; US 5574069; US 5698596; US 5776980 . |
| 【1】 Martin, L.; Mealy, N.M.; Castaner, J.; Clamikalant sodium. Drugs Fut 2001, 26, 10, 951. |
| 【2】 Gerlach, U.; Scheidler, S.; Mania, D.; Heitsch, H.; Goegelein, H.; Hartung, J.; Englert, H.C.; Cardioselective KATP channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem 2001, 44, 7, 1085. |
| 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) | 48701 | 1-(p-Methoxyphenyl)ethylamine; 1-Amino-2-(4-methoxyphenyl)ethane; 2-(4-Methoxyphenyl)ethylamine; 4-(2-Aminoethyl)anisole; 4-Methoxybenzeneethanamine; 4-Methoxyphenethylamine; 4-Methoxyphenylethylamine; p-Methoxy phenethylamine; p-Methoxy phenylethylamine | 55-81-2 | C9H13NO | 详情 | 详情 |
| (II) | 48702 | 5-Chloro-2-methoxybenzoic acid; 5-Chloro-o-anisic acid | 3438-16-2 | C8H7ClO3 | 详情 | 详情 |
| (III) | 44240 | 5-chloro-2-methoxybenzoyl chloride | C8H6Cl2O2 | 详情 | 详情 | |
| (IV) | 48703 | 5-chloro-2-methoxy-N-(4-methoxyphenethyl)benzamide | C17H18ClNO3 | 详情 | 详情 | |
| (V) | 48704 | 5-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]-2-methoxybenzenesulfonyl chloride | C17H17Cl2NO5S | 详情 | 详情 | |
| (VI) | 48705 | N-[3-(aminosulfonyl)-4-methoxyphenethyl]-5-chloro-2-methoxybenzamide | C17H19ClN2O5S | 详情 | 详情 | |
| (VII) | 12092 | Methyl isothiocyanate; MITC; (Methylimino)(thioxo)methane | 556-61-6 | C2H3NS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Coupling between ethylamine derivative (I) and acid chloride (II) by means of DMAP in pyridine affords benzamide (III), which is then subjected to reaction with chlorosulfonic acid followed by treatment with aqueous ammonia to provide benzenesulfonamide (IV). Finally, the desired product is obtained by condensation of (IV) with methyl isothiocyanate in DMF by means of K2CO3.
| 【1】 Gögelein, H.; Bohn, H.; Heitsch, H.; Englert, H.C.; Gerlach, U.; Wirth, K. (Aventis Pharma Deutschland GmbH); Use of benzenesulfonyl(thio)ureas for the treatment and prophylaxis of dysfunctions of the autonomous nervous system and use of benzenesulfonyl(thio)ureas in combination with beta-receptor blockers. DE 19841534; EP 1117409; WO 0015204 . |
| 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) | 48701 | 1-(p-Methoxyphenyl)ethylamine; 1-Amino-2-(4-methoxyphenyl)ethane; 2-(4-Methoxyphenyl)ethylamine; 4-(2-Aminoethyl)anisole; 4-Methoxybenzeneethanamine; 4-Methoxyphenethylamine; 4-Methoxyphenylethylamine; p-Methoxy phenethylamine; p-Methoxy phenylethylamine | 55-81-2 | C9H13NO | 详情 | 详情 |
| (II) | 50166 | 5-(tert-butyl)-2-methoxybenzoyl chloride | C12H15ClO2 | 详情 | 详情 | |
| (III) | 50167 | 5-(tert-butyl)-2-methoxy-N-(4-methoxyphenethyl)benzamide | C21H27NO3 | 详情 | 详情 | |
| (IV) | 50168 | N-[3-(aminosulfonyl)-4-methoxyphenethyl]-5-(tert-butyl)-2-methoxybenzamide | C21H28N2O5S | 详情 | 详情 |