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【结 构 式】 
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【分子编号】22234 【品名】cycloheptanamine; cycloheptylamine 【CA登记号】5452-35-7 |
【 分 子 式 】C7H15N 【 分 子 量 】113.20284 【元素组成】C 74.27% H 13.36% N 12.37% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of cycloheptylamine (I) with triethyl orthoformate (II) and diethyl phosphite (III) at 150 gives cycloheptylaminomethylenediphosphonic acid tetraethyl ester (IV), which is then hydrolyzed with refluxing concentrated hydrochloric acid.
| 【1】 Isomura, Y.; Takeuchi, M.; Sakamoto, S.; Abe, T. (Yamanouchi Pharmaceutical Co., Ltd.); (Cycloalkylamino)methylenebisphosphonic acids and medicines containing them. AU 8928670; EP 0325482; JP 1989308290; US 5041428 . |
| 【2】 Takeuchi, M.; Sakamoto, S.; Kawamuki, K.; Kudo, M.; Murase, K.; Kawashima, H.; Isomura, Y.; Synthesis and structure-activity relationships of a novel anti-resorptive agent YM175, and the related derivatives. Symp Med Chem 1990, P-12. |
| 【3】 Prous, J.; Castaner, J.; YM-175. Drugs Fut 1992, 17, 4, 293. |
| 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) | 22234 | cycloheptanamine; cycloheptylamine | 5452-35-7 | C7H15N | 详情 | 详情 |
| (II) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (III) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (IV) | 31262 | diethyl [bis(2-hydroxyethyl)phosphoryl](cycloheptylamino)methylphosphonate | C16H35NO6P2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)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3
该中间体在本合成路线中的序号：(IV)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 |
合成路线4
该中间体在本合成路线中的序号：(II)The title phthalimide derivative was prepared by condensation of tetrachlorophthalic anhydride (I) with cycloheptylamine (II) in refluxing pyridine.
| 【1】 Sou, S.; et al.; alpha-Glucosidase inhibitors with a 4,5,6,7-tetrachlorophthalimide skeleton pendanted with a cycloalkyl or dicarba-closo-dodecaborane group. Chem Pharm Bull 2001, 49, 6, 791. |