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【结 构 式】

【药物名称】

【化学名称】1-[4-(3,5-Dibromo-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-(1-oxidopyridin-4-yl)ethanone

【CA登记号】

【 分 子 式 】C26H22Br2ClN3O2

【 分 子 量 】603.74514

【开发单位】Schering-Plough (Originator)

【药理作用】ONCOLYTIC DRUGS, Farnesyl Transferase Inhibitors

合成路线1

Isomerization of (I) in refluxing trifluoromethanesulfonic acid provided the endocyclic olefin (II). Further reaction with ethyl chloroformate and triethylamine in toluene gave carbamate (III), which was then nitrated with a cooled mixture tetra-n-butylammonium nitrate and trifluoroacetic anhydride in dicloromethane, to afford a mixture of nitrocompounds (IV) and (V). After separation by column chromatography on silica gel, nitrocompound (V )was reduced with iron powder and calcium chloride in refluxing aqueous ethanol to amine (VII). Diazotization of amine (VII) with NaNO2 in 48% HBr in the presence of bromine at -5 C gave a mixture of monobromide (VIII) and dibromide (IX), which were separated on column chromatography. The dibromocarbamate (IX) was hydrolyzed in refluxing HCl to amine (X), which was finally coupled with 4-pyridylacetic acid N-oxide (XI) by treatment with EDC and HOBT.

1 Njoroge, F.G.; et al.; Potent, selective, and orally bioavailable tricyclic pyridyl acetamide N-oxide inhibitors of farnesyl protein transferase with enhanced in vivo antitumor activity. J Med Chem 1998, 41, 10, 1561.
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) 17840 8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine C19H19ClN2 详情 详情
(II) 17841 8-chloro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine C19H19ClN2 详情 详情
(III) 17842 ethyl 4-(8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate C22H23ClN2O2 详情 详情
(IV) 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
(V) 17844 ethyl 4-(8-chloro-3-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate C22H22ClN3O4 详情 详情
(VII) 17845 ethyl 4-(3-amino-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate C22H24ClN3O2 详情 详情
(VIII) 17846 ethyl 4-(3-bromo-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate C22H22BrClN2O2 详情 详情
(IX) 17847 ethyl 4-(3,5-dibromo-8-chloro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate C22H21Br2ClN2O2 详情 详情
(X) 17848 3,5-dibromo-8-chloro-11-(4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine C19H17Br2ClN2 详情 详情
(XI) 17849 2-(1-hydroxy-1lambda(5)-pyridin-4-yl)acetic acid C7H9NO3 详情 详情
Extended Information