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【结 构 式】 
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【药物名称】Sch-59948 【化学名称】8-Chloro-11-[1-[2-(4-pyridyl)acetyl]piperidin-4-yl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-6-one oxime 【CA登记号】 【 分 子 式 】C26H25ClN4O2 【 分 子 量 】460.96775 |
【开发单位】Schering-Plough (Originator) 【药理作用】Oncolytic Drugs, Farnesyl Transferase Inhibitors |
合成路线1
Carbamate (I) was hydrolyzed to amine (II) by treatment with an ethanolic solution of HCl, which was then isomerized to the endocyclic compound (III) on heating with trifluoromethanesulfonic acid. Compound III was protected as the carbamate (IV) by reaction with ethyl chloroformate, and further nitration was effected with tetra-n-butylammonium nitrate - trifluoroacetic anhydride (TFAA) reagent to afford nitro compound (V). Subsequent deprotection of carbamate was effected with ethanolic HCl, to give amine (VI), which was then condensed with 4-pyridylacetic acid (VII) to the amide (VIII). Reduction of the nitro group of (VIII) with tin (II) chloride yielded oxime (IX) (SCH 59948), and reaction of this compound with acetyl chloride gave the corresponding oxime acetate (SCH 60102).
| 【1】 del Rosario, J.D.; et al.; Benzocycloheptapyridine farnesyl protein transferase inhibitors: Effects of substitution at position 5 and 6 on enzyme inhibition. 213th ACS Natl Meet (April 13-17, San Francisco) 1997, Abst MEDI 198. |
| 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) | 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 |
| (II) | 17840 | 8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C19H19ClN2 | 详情 | 详情 | |
| (III) | 17841 | 8-chloro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine | C19H19ClN2 | 详情 | 详情 | |
| (IV) | 17842 | ethyl 4-(8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate | C22H23ClN2O2 | 详情 | 详情 | |
| (V) | 17843 | ethyl 4-(8-chloro-6-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate | C22H22ClN3O4 | 详情 | 详情 | |
| (VI) | 17882 | 8-chloro-6-nitro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine | C19H18ClN3O2 | 详情 | 详情 | |
| (VII) | 17883 | 2-(4-pyridinyl)acetic acid | 28356-58-3 | C7H7NO2 | 详情 | 详情 |
| (VIII) | 17884 | 1-[4-(8-chloro-6-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinyl]-2-(4-pyridinyl)-1-ethanone | C26H23ClN4O3 | 详情 | 详情 | |
| (IX) | 17885 | 8-chloro-11-[1-[2-(4-pyridinyl)acetyl]-4-piperidinyl]-5,11-dihydro-6H-benzo[5,6]cyclohepta[1,2-b]pyridin-6-one oxime | C26H25ClN4O2 | 详情 | 详情 |