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【结 构 式】 
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【分子编号】11926 【品名】1-[4-(Chloromethyl)-2-hydroxy-3-propylphenyl]-1-ethanone 【CA登记号】 |
【 分 子 式 】C12H15ClO2 【 分 子 量 】226.7026 【元素组成】C 63.58% H 6.67% Cl 15.64% O 14.11% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 4-acetyl-3-hydroxy-2-propylbenzyl chloride (I) with 2,5-dimercapto-1,3,4-thiadiazole (II) in 2-butanone gives 2-[(4-acetyl-3-hydroxy-2-propylbenzyl)thio]-5-mercapto-1,3,4-thiadiazole (III), which is condensed with alpha-bromo-p-toluic acid (IV) in 2-butanone.
| 【1】 Mase, T.; Murase, K.; Tsuzuki, R.; Tomioka, K.; Hara, H. (Yamanouchi Pharmaceutical Co., Ltd.); (Substd. benzyl)thio heterocyclic cpds. having leukotriene-antagonist activity. EP 0214732; US 4803211; US 4933348; US 5180730 . |
| 【2】 Yamada, T.; Tomioka, K.; Mase, T.; YM-17551. Drugs Fut 1990, 15, 9, 905. |
| 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) | 11926 | 1-[4-(Chloromethyl)-2-hydroxy-3-propylphenyl]-1-ethanone | C12H15ClO2 | 详情 | 详情 | |
| (II) | 11927 | 5-Sulfanyl-1,3,4-thiadiazol-2-ylhydrosulfide; 1,3,4-Thiadiazole-2,5-dithiol | 1072-71-5 | C2H2N2S3 | 详情 | 详情 |
| (III) | 11928 | 1-(2-Hydroxy-3-propyl-4-[[(5-sulfanyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]phenyl)-1-ethanone | C14H16N2O2S3 | 详情 | 详情 | |
| (IV) | 11929 | 4-(Bromomethyl)benzoic acid; alpha-Bromo-p-toluic acid | 6232-88-8 | C8H7BrO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Reaction of isophthaloyl dichloride (I) with cycloheptylamine (II) in the presence of triethylamine in dichloromethane gives N,N'-dicycloheptylisophthalimide (III), which is reduced with sodium bis(2-methoxyethoxy)aluminum hydride in toluene to yield 1,3-bis(cycloheptylaminomethyl)benzene (IV). Compound (IV) is treated with p-nitrophenylisocyanate (V) to afford 1,3-bis[1-cycloheptyl-3-(4-nitrophenyl)ureidomethyl]benzene (VI), which is reduced with hydrogen in the presence of palladium over charcoal to give 1,3-bis[1-cycloheptyl-3-(4-aminophenyl)ureidomethyl]benzene (VII). Finally, compound (VII) is treated with aqueous formaldehyde and hydrogen in the presence of platinum oxide in ethanol, followed by addition of hydrochloric acid in ethanol.
| 【1】 Ito, N.; Yasunaga, T.; Iizumi, Y.; Araki, T. (Yamanouchi Pharmaceutical Co., Ltd.); Diurea derivatives useful as medicaments and processes for the preparation thereof. AU 8928669; EP 0325397; JP 1990117651; US 5091419; US 5166429; US 5384425 . |
| 【2】 Yasunaga, T.; Araki, T.; Iwaoka, K.; Iizumi, Y.; Ohata, I.; Matsuda, K.; Ito, N.; Synthesis and activity of a novel phenylenediurea derivative with hypolipidemic and antiatherosclerotic activity. 111th Annu Meet Pharmaceut Soc Jpn (March 28-30, Tokyo) 1991, Abst 29V 3-040.. |
| 【3】 Graul, A.; Castaner, J.; Prous, J.; YM17E. Drugs Fut 1993, 18, 9, 813. |
| 【4】 Iizumi, Y.; Ohhata, I.; Iwaoka, K.; Matsuda, K.; Ito, N.; Yasunaga, T.; Araki, T.; Synthesis and hypocholesterolemic activity of phenylene and pyridylene diurea derivatives as ACAT inhibitors. 202nd ACS Natl Meet (Aug 25-30, New York) 1991, Abst MEDI 109. |
| 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) | 12501 | Isophthaloyl dichloride | 99-63-8 | C8H4Cl2O2 | 详情 | 详情 |
| (II) | 11926 | 1-[4-(Chloromethyl)-2-hydroxy-3-propylphenyl]-1-ethanone | C12H15ClO2 | 详情 | 详情 | |
| (III) | 14907 | N(1),N(3)-dicycloheptylisophthalamide | C22H32N2O2 | 详情 | 详情 | |
| (IV) | 14908 | N-cycloheptyl-N-[3-[(cycloheptylamino)methyl]benzyl]amine; N-[3-[(cycloheptylamino)methyl]benzyl]cycloheptanamine | C22H36N2 | 详情 | 详情 | |
| (V) | 14909 | 1-isocyanato-4-nitrobenzene; 4-Nitrophenyl isocyanate | 100-28-7 | C7H4N2O3 | 详情 | 详情 |
| (VI) | 14910 | N-cycloheptyl-N-[3-([cycloheptyl[(4-nitroanilino)carbonyl]amino]methyl)benzyl]-N'-(4-nitrophenyl)urea | C36H44N6O6 | 详情 | 详情 | |
| (VII) | 14911 | N-(3-[[[(4-aminoanilino)carbonyl](cycloheptyl)amino]methyl]benzyl)-N'-(4-aminophenyl)-N-cycloheptylurea | C36H48N6O2 | 详情 | 详情 |