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【结 构 式】 
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【分子编号】16506 【品名】8-chloro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinyl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol 【CA登记号】 |
【 分 子 式 】C26H28ClN3O 【 分 子 量 】433.98064 【元素组成】C 71.96% H 6.5% Cl 8.17% N 9.68% O 3.69% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 2-cyano-3-methylpyridine (I) with H2SO4 in t-BuOH gives the N-tert-butylamide (II), which is treated with two equivalents of BuLi and the corresponding dianion alkylated with 3-chlorobenzyl chloride to afford amide (III). The treatment of (III) with POCl3 gives nitrile (IV), which is cyclized to ketone (V) by subsequent treatment with CF3SO3H and aqueous HCl. Reaction of ketone (V) with the Grignard derivative prepared from chloride (VI) affords alcohol (VII), which is finally dehydrated by H2SO4 to give UR-12592, as shown in Scheme 20491401a.
| 【1】 Carceller, E.; Jiménez, P.J.; Salas, J. (J. Uriach & Cia., SA); Process for the preparation of 8-chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine. ES 9602107 . |
| 【2】 García-Rafanell, J.; Rupatadine Fumarate. Drugs Fut 1996, 21, 10, 1032. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 20642 | 1-chloro-3-(chloromethyl)benzene; 3-Chlorobenzyl chloride | 620-20-2 | C7H6Cl2 | 详情 | 详情 | |
| (I) | 16500 | 3-methyl-2-pyridinecarbonitrile | 20970-75-6 | C7H6N2 | 详情 | 详情 |
| (II) | 16501 | N-(tert-butyl)-3-methyl-2-pyridinecarboxamide | C11H16N2O | 详情 | 详情 | |
| (III) | 20643 | N-(tert-butyl)-3-(3-chlorophenethyl)-2-pyridinecarboxamide | C18H21ClN2O | 详情 | 详情 | |
| (IV) | 20644 | 3-(3-chlorophenethyl)-2-pyridinecarbonitrile | C14H11ClN2 | 详情 | 详情 | |
| (V) | 16504 | 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one; 8-Chloro-10,11-dihydro-4-aza-5H-dibenzo[a,d]cycloheptan-5-one | 31251-41-9 | C14H10ClNO | 详情 | 详情 |
| (VI) | 16505 | 4-chloro-1-[(5-methyl-3-pyridinyl)methyl]piperidine | C12H17ClN2 | 详情 | 详情 | |
| (VII) | 16506 | 8-chloro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinyl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol | C26H28ClN3O | 详情 | 详情 |