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【结 构 式】 
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【分子编号】43692 【品名】26-formyl-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),1(29),2,4,9,19,21,25,27-nonaen-13-yl acetate 【CA登记号】 |
【 分 子 式 】C38H47NO13 【 分 子 量 】725.79012 【元素组成】C 62.89% H 6.53% N 1.93% O 28.66% |
合成路线1
该中间体在本合成路线中的序号：(VI)The cyclization of piperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives perhydropyrido[1,2-a]pyrazin-1-one (III), which is reduced with LiAlH4 to yield perhydropyrido[1,2-a]pyrazine (IV). The reaction of (IV) with NaNO2/HCl, followed by reduction with LiAlH4, affords perhydropyrido[1,2-a]pyrazin-2-amine (V), which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
| 【1】 Hauffe, S.; Tosch, W.; Batt, E.; Ashtekar, D.R.; Costa-Pereira, R.; Vischer, W.; Traxler, P.; Degen, P.; Zak, O.; Imhof, P.; Gowrishankar, R.; 3-Formylrifamycin SV-hydrazones with diazabicycloalkyl side-chains: New rifamycins aganist tuberculosis with long plasma half-lives. 27th Intersci Conf Antimicrob Agents Chemother 1987, Abst 278. |
| 【2】 Ashtekar, D.R.; Vischer, W.; Kump, W.; Costa-Pereira, R.; Traxler, P.; Subrahmanyam, D.; Gowrishankar, R.; Antitubercular activity in vitro and in vivo of new long-acting rifamycin derivatives. Bull Intl Union Tuberc 1986, 61, 3, 8. |
| 【3】 Traxler, P. (Novartis Corp.); Novel polycyclic hydrazones of rifamycins, their manufacture, and their pharmaceutical compsns. for treating tuberculosis. US 4681938 . |
| 【4】 Traxler, P.; Vischer, W.; Zak, O.; New Rifamycins. Drugs Fut 1988, 13, 9, 845. |
| 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) | 43693 | ethyl 2-piperidinecarboxylate | 15862-72-3 | C8H15NO2 | 详情 | 详情 |
| (II) | 10151 | Ethyleneimine; Aziridine; Azirane | 151-56-4 | C2H5N | 详情 | 详情 |
| (III) | 43694 | hexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one | C8H14N2O | 详情 | 详情 | |
| (IV) | 43695 | octahydro-2H-pyrido[1,2-a]pyrazine | C8H16N2 | 详情 | 详情 | |
| (V) | 43696 | octahydro-2H-pyrido[1,2-a]pyrazin-2-ylamine; octahydro-2H-pyrido[1,2-a]pyrazin-2-amine | C8H17N3 | 详情 | 详情 | |
| (VI) | 43692 | 26-formyl-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),1(29),2,4,9,19,21,25,27-nonaen-13-yl acetate | C38H47NO13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The cyclization of 5-ethylpiperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives 7-ethylperhydropyrido[1,2-a]pyrazin-1-one (III), which is reduced with LiAlH4 to yield 7-ethylperhydropyrido[1,2-a]pyrazine (IV). The reaction of (IV) with NaNO2/HCl, followed by reduction with LiAlH4, affords 7-ethylperhydropyrido[1,2-a]pyrazin-2-amine (V), which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
| 【1】 Hauffe, S.; Tosch, W.; Batt, E.; Ashtekar, D.R.; Costa-Pereira, R.; Vischer, W.; Traxler, P.; Degen, P.; Zak, O.; Imhof, P.; Gowrishankar, R.; 3-Formylrifamycin SV-hydrazones with diazabicycloalkyl side-chains: New rifamycins aganist tuberculosis with long plasma half-lives. 27th Intersci Conf Antimicrob Agents Chemother 1987, Abst 278. |
| 【2】 Traxler, P. (Novartis Corp.); Novel polycyclic hydrazones of rifamycins, their manufacture, and their pharmaceutical compsns. for treating tuberculosis. US 4681938 . |
| 【3】 Traxler, P.; Vischer, W.; Zak, O.; New Rifamycins. Drugs Fut 1988, 13, 9, 845. |
| 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) | 43688 | ethyl 5-ethyl-2-piperidinecarboxylate | C10H19NO2 | 详情 | 详情 | |
| (II) | 10151 | Ethyleneimine; Aziridine; Azirane | 151-56-4 | C2H5N | 详情 | 详情 |
| (III) | 43689 | 7-ethylhexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one | C10H18N2O | 详情 | 详情 | |
| (IV) | 43690 | 7-ethyloctahydro-2H-pyrido[1,2-a]pyrazine | C10H20N2 | 详情 | 详情 | |
| (V) | 43691 | 7-ethyloctahydro-2H-pyrido[1,2-a]pyrazin-2-amine; 7-ethyloctahydro-2H-pyrido[1,2-a]pyrazin-2-ylamine | C10H21N3 | 详情 | 详情 | |
| (VI) | 43692 | 26-formyl-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),1(29),2,4,9,19,21,25,27-nonaen-13-yl acetate | C38H47NO13 | 详情 | 详情 |