|
【结 构 式】 
|
【药物名称】Sch-69956 [(-)-(S)-isomer], Sch-69955 [(+)-(R)-isomer], Sch-54429 【化学名称】(±)-8-Chloro-11-[4-[2-(4-pyridyl)acetyl]piperazin-1-yl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine 【CA登记号】169250-83-3 【 分 子 式 】C25H25ClN4O 【 分 子 量 】432.9572 |
【开发单位】Schering-Plough (Originator) 【药理作用】ONCOLYTIC DRUGS, Farnesyl Transferase Inhibitors |
合成路线1
Ketone (I) was reduced with sodium borohydride in methanol to alcohol (II), which was then converted into chloride (III) on treatment with thionyl chloride in cooled toluene. Alkylation of piperazine (IV) with chloride (III) in the presence of triethylamine gave V. Finally, piperazine (V) was condensed with 4-pyridylacetic acid (VI) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (DEC), 1-hydroxybenzotriazole (HOBt), and N-methylmorpholine in DMF to afford the target amide.
| 【1】 Lesur, B.; et al.; New deoxynojirimycin derivatives as potent inhibitors of intestinal alpha-glucohydrolases. Bioorg Med Chem Lett 1997, 7, 3, 355-360. |
| 【2】 Lesur, B.; Ducep, J.-B.; Danzin, C. (Merrell Pharmaceuticals, Inc.); Novel nojirimycin derivs.. EP 0453692; EP 0454580; JP 1993086072; US 5252587; US 5536732 . |
| 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) | 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 |
| (II) | 17935 | 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol | C14H12ClNO | 详情 | 详情 | |
| (III) | 17936 | 8,11-dichloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C14H11Cl2N | 详情 | 详情 | |
| (IV) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (V) | 17938 | 8-chloro-11-(1-piperazinyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C18H20ClN3 | 详情 | 详情 | |
| (VI) | 17883 | 2-(4-pyridinyl)acetic acid | 28356-58-3 | C7H7NO2 | 详情 | 详情 |