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【结 构 式】 
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【分子编号】63971 【品名】methyl 3-[4-(2-{4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl}-2-oxoethyl)-1-piperidinyl]-3-oxopropanoate 【CA登记号】 |
【 分 子 式 】C30H34Br2ClN3O4 【 分 子 量 】695.87848 【元素组成】C 51.78% H 4.92% Br 22.96% Cl 5.09% N 6.04% O 9.2% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Amine (VII) is coupled to N-Boc-4-piperidineacetic acid (VIII) by means of EDC/HOBt to afford amide (IX). Subsequent acidic cleavage of the N-Boc group of (IX) leads to amine (X) (1,2). Piperidine (X) is finally coupled with malonic acid mono-amide (XI) to furnish the title compound (1,2). In a related method, piperidine (X) is coupled to mono-methyl malonate (XII), yielding the amide ester (XIII). Basic hydrolysis of the methyl ester group of (XIII) then leads to the sodium carboxylate salt (XIV), which is finally reacted with ammonium chloride in the presence of EDC/HOBt to produce the target amide (3).
| 【1】 Njoroge, F.G.; Vibulbhan, B.; Pinto, P.; Strickland, C.L.; Bishop, W.R.; Kirschmeir, P.; Girijavallabhan, V.; Ganguly, A.K.; Trihalobenzocycloheptapyridine analogues of Sch 66336 as potent inhibitors of farnesyl protein transferase. Bioorg Med Chem 2003, 11, 1, 139. |
| 【2】 Doll, R.J.; Njoroge, F.G.; Remiszewski, S.W.; Taveras, A.G.; Lalwani, T.; Alvarez, C. (Schering Corp.); Cpds. useful for inhibition of farnesyl protein transferase. US 6030982 . |
| 【3】 Doll, R.J.; Njoroge, F.G.; Remiszewski, S.W.; Taveras, A.G.; Lalwani, T.; Alvarez, C. (Schering Corp.); Cpds. useful for inhibition of farnesyl protein transferase. WO 9830558 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 19345 | (11R)-3,10-dibromo-8-chloro-11-(4-piperidinyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine | C19H19Br2ClN2 | 详情 | 详情 | |
| (VIII) | 19346 | 1-Boc-piperidin-4-ylacetic acid; 2-[1-(tert-butoxycarbonyl)-4-piperidinyl]acetic acid | 157688-46-5 | C12H21NO4 | 详情 | 详情 |
| (IX) | 19347 | tert-butyl 4-(2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl)-1-piperidinecarboxylate | C31H38Br2ClN3O3 | 详情 | 详情 | |
| (X) | 19348 | 1-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-(4-piperidinyl)-1-ethanone | C26H30Br2ClN3O | 详情 | 详情 | |
| (XI) | 63973 | 3-oxo-beta-alanine | C3H5NO3 | 详情 | 详情 | |
| (XII) | 16198 | 3-Methoxy-3-oxopropionic acid; Malonic acid monomethyl ester | 16695-14-0 | C4H6O4 | 详情 | 详情 |
| (XIII) | 63971 | methyl 3-[4-(2-{4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl}-2-oxoethyl)-1-piperidinyl]-3-oxopropanoate | C30H34Br2ClN3O4 | 详情 | 详情 | |
| (XIV) | 63972 | sodium 3-[4-(2-{4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl}-2-oxoethyl)-1-piperidinyl]-3-oxopropanoate | C29H31Br2ClN3NaO4 | 详情 | 详情 |