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【结 构 式】 
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【分子编号】68542 【品名】N-(4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)acetamide 【CA登记号】 |
【 分 子 式 】C16H29N3O 【 分 子 量 】279.426 【元素组成】C 68.78% H 10.46% N 15.04% O 5.73% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)Condensation of 4-acetamidocyclohexanone (XVII) with N-(cyclopropylmethyl)piperazine (VI) in refluxing toluene, optionally in the presence of MsOH , followed by reduction by means of NaBH4 or H2 over PtO2 in EtOH yields the trans-diaminocyclohexane derivative (XVIII) . Hydrolysis of acetamide (XVIII) using either boiling aqueous HCl or p-TsOH in H2O at 120 °C in a sealed reactor gives the corresponding cyclohexylamine trihydrochloride (XXa) or tritosylate salt (XXb) (1-3). Finally, compounds (XIXa) or (XIXb) are acylated with 3-methoxy-4-nitrobenzoyl chloride (II) in the presence of DIEA in THF or aqueous NaOH .
| 【1】 Grauert, M., Linz, G., Schmid, R., Sieger, P. (Boehringer Ingelheim Pharma GmbH & Co. KG). Trihydrochloride forms of a dihydropteridinone derivative and process for preparation. WO 2007090844. |
| 【2】 Linz, G., Kraemer, G.F., Gutschera, L., Asche, G. (Boehringer Ingelheim International GmbH). Method for the production of dihydropteridinones. WO 2006018220. |
| 【3】 Schnaubelt, J., Herter, R. (Boehringer Ingelheim International GmbH). Process for manufacturing dihydropteridinones and intermediates thereof. WO 2012049153. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIXa) | 68543 | 4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexanamine trihydrochloride | C14H27N3.3HCl | 详情 | 详情 | |
| (XIXb) | 68544 | 4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexanamine tris(4-methylbenzenesulfonate) | C14H27N3.3C7H8O3S | 详情 | 详情 | |
| (II) | 21086 | 3-methoxy-4-nitrobenzoyl chloride | C8H6ClNO4 | 详情 | 详情 | |
| (VI) | 68532 | N-(cyclopropylmethyl)piperazine；1-(Cyclopropylmethyl)piperazine | 57184-25-5 | C8H16N2 | 详情 | 详情 |
| (VII) | 68533 | N-((1r,4r)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxy-4-nitrobenzamide | C22H32N4O4 | 详情 | 详情 | |
| (XVII) | 11895 | N-(4-Oxocyclohexyl)acetamide | 27514-08-5 | C8H13NO2 | 详情 | 详情 |
| (XVIII) | 68542 | N-(4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)acetamide | C16H29N3O | 详情 | 详情 |