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【结 构 式】 
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【分子编号】17844 【品名】ethyl 4-(8-chloro-3-nitro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C22H22ClN3O4 【 分 子 量 】427.8872 【元素组成】C 61.76% H 5.18% Cl 8.29% N 9.82% O 14.96% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |