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【结 构 式】 
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【分子编号】22235 【品名】N-cycloheptyl-N-[4-(4-fluorophenoxy)benzyl]amine; N-[4-(4-fluorophenoxy)benzyl]cycloheptanamine 【CA登记号】 |
【 分 子 式 】C20H24FNO 【 分 子 量 】313.4151032 【元素组成】C 76.65% H 7.72% F 6.06% N 4.47% O 5.1% |
合成路线1
该中间体在本合成路线中的序号：(VI)Condensation of 4-bromobenzaldehyde (I) with 4-fluorophenol (II) in the presence of K2CO3 in refluxing dimethylacetamide gave ether (III). Subsequent reductive amination of (III) with cycloheptylamine (IV) using ethanolic NaBH4 afforded secondary amine (V). Phenyl carbamate (VIII) was obtained by treatment of aminopyridine (VI) with phenyl chloroformate (VII) and dimethylaniline. Condensation of this carbamate with amine (V) in the presence of Et3N in refluxing toluene furnished urea (IX) (1). Both sulfide groups of (IX) were finally oxidized to sulfone using meta-chloroperbenzoic acid in CH2Cl2.
| 【1】 Tanaka, A.; Terasawa, T.; Hagihara, H.; Ishibe, N.; Sawada, M.; Sakuma, Y.; Hashimoto, M.; Takasugi, H.; Tanaka, H.; Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 3. Discovery of a novel series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas with weak toxicological effects on adrenal glands. J Med Chem 1998, 41, 22, 4408. |
| 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) | 22231 | 4-Bromobenzaldehyde | 1122-91-4 | C7H5BrO | 详情 | 详情 |
| (II) | 19639 | 4-fluorophenol | 371-41-5 | C6H5FO | 详情 | 详情 |
| (III) | 22233 | 4-(4-fluorophenoxy)benzaldehyde | C13H9FO2 | 详情 | 详情 | |
| (IV) | 22234 | cycloheptanamine; cycloheptylamine | 5452-35-7 | C7H15N | 详情 | 详情 |
| (VI) | 22235 | N-cycloheptyl-N-[4-(4-fluorophenoxy)benzyl]amine; N-[4-(4-fluorophenoxy)benzyl]cycloheptanamine | C20H24FNO | 详情 | 详情 | |
| (VI) | 22239 | 6-methyl-2,4-bis(methylsulfanyl)-3-pyridinylamine; 6-methyl-2,4-bis(methylsulfanyl)-3-pyridinamine | C8H12N2S2 | 详情 | 详情 | |
| (VII) | 13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 |
| (VIII) | 18000 | phenyl 6-methyl-2,4-bis(methylsulfanyl)-3-pyridinylcarbamate | C15H16N2O2S2 | 详情 | 详情 | |
| (IX) | 22241 | N-cycloheptyl-N-[4-(4-fluorophenoxy)benzyl]-N'-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]urea | C29H34FN3O2S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Condensation of 4-bromobenzaldehyde (I) with 4-fluorophenol (II) in the presence of K2CO3 in refluxing dimethylacetamide gave ether (III). Subsequent reductive amination of (III) with cycloheptylamine (IV) using ethanolic NaBH4 afforded secondary amine (V). Phenyl carbamate (VIII) was obtained by treatment of aminopyridine (VI) with phenyl chloroformate (VII) and dimethylaniline. Finally, condensation of this carbamate with amine (V) in the presence of Et3N in DMF at 100 C furnished the target urea.
| 【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 . |
| 【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 . |
| 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) | 22231 | 4-Bromobenzaldehyde | 1122-91-4 | C7H5BrO | 详情 | 详情 |
| (II) | 19639 | 4-fluorophenol | 371-41-5 | C6H5FO | 详情 | 详情 |
| (III) | 22233 | 4-(4-fluorophenoxy)benzaldehyde | C13H9FO2 | 详情 | 详情 | |
| (IV) | 22234 | cycloheptanamine; cycloheptylamine | 5452-35-7 | C7H15N | 详情 | 详情 |
| (V) | 22235 | N-cycloheptyl-N-[4-(4-fluorophenoxy)benzyl]amine; N-[4-(4-fluorophenoxy)benzyl]cycloheptanamine | C20H24FNO | 详情 | 详情 | |
| (VI) | 22236 | 2,4,6-trimethyl-3-pyridinylamine; 2,4,6-trimethyl-3-pyridinamine | C8H12N2 | 详情 | 详情 | |
| (VII) | 13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 |
| (VIII) | 22238 | phenyl 2,4,6-trimethyl-3-pyridinylcarbamate | C15H16N2O2 | 详情 | 详情 |