|
【结 构 式】 
|
【药物名称】Sch-37370 【化学名称】11-(1-Acetyl-4-piperidylidene)-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine 【CA登记号】117796-52-8 【 分 子 式 】C21H21ClN2O 【 分 子 量 】352.86732 |
【开发单位】Schering-Plough (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Histamine H1 Antagonists, Non-Steroidal Antiinflammatory Drugs, Platelet-Activating Factor (PAF) Antagonists |
合成路线1
N-tert-Butyl-3-methyl-2-pyridinecarboxamide (I) was treated with two equivalents of butyllithium at -40 C, and the resulting dianion was C-alkylated with 3-chlorobenzyl chloride (II) to provide the phenetylpyridine (III). Further refluxing with phosphoryl chloride afforded nitrile (IV), which was condensed with the piperidinyl Grignard reagent (V) to yield, after hydrolysis, ketone (VI). Acid-catalyzed cyclization of ketone (VI) produced the tricyclic compound (VII). Demethylation was then accomplished by conversion to the ethyl carbamate (VIII) by treatment with ethyl chloroformate, followed by hydrolysis to the N-unsubstituted piperidine (IX). Finally, acetylation of (IX) in the presence of pyridine provided the target amide.
| 【1】 Billah, M.M.; Green, M.J.; Wong, J.K.; Piwinski, J.J.; West, R.E. Jr.; Ganguly, A.K.; Kreutner, W.; Dual antagonists of platelet activating factor and histamine. Identification of structural requirements for dual activity of N-acyl-4-(5,6-dihydro-11H-benzo[5,6]cyclohepta-[1,2-b]pyridin-11-ylidene)piperidines. J Med Chem 1991, 34, 1, 457. |
| 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) | 16501 | N-(tert-butyl)-3-methyl-2-pyridinecarboxamide | C11H16N2O | 详情 | 详情 | |
| (II) | 20642 | 1-chloro-3-(chloromethyl)benzene; 3-Chlorobenzyl chloride | 620-20-2 | C7H6Cl2 | 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) | 20645 | chloro(1-methyl-4-piperidinyl)magnesium | C6H12ClMgN | 详情 | 详情 | |
| (VI) | 20646 | [3-(3-chlorophenethyl)-2-pyridinyl](1-methyl-4-piperidinyl)methanone | C20H23ClN2O | 详情 | 详情 | |
| (VII) | 20647 | 8-chloro-11-(1-methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | 38092-89-6 | C20H21ClN2 | 详情 | 详情 |
| (VIII) | 17877 | ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate | 79794-75-5 | C22H23ClN2O2 | 详情 | 详情 |
| (IX) | 17840 | 8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C19H19ClN2 | 详情 | 详情 |