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【结 构 式】 
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【分子编号】31880 【品名】(5S,6S)-6-(acetamido)-5-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)-1-(2-ethylbutanoyl)-1,4,5,6-tetrahydro-3-pyridazinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C24H40N6O8 【 分 子 量 】540.61724 【元素组成】C 53.32% H 7.46% N 15.55% O 23.68% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reaction of imidazole (I) with tert-butoxycarbonyl anhydride in ethyl acetate, followed by acetylation with acetic anhydride gives the cis-ethylenediamine derivative (II), which is isomerized to its trans isomer (III) with I2 in THF. The cyclization of (III) with hydrazone (IV) by means of Na2CO3 in hot acetonitrile yields the tetrahydropyridazine (V), which s deprotected at the amino group with HCl in ethyl acetate affording the amine (VI). The condensation of (VI) with the protected thiourea (VII) by means of HgCl2 and Et3N in DMF gives the protected guanidine (VIII), which is hydrolyzed at the ester group with KOH in methanol/water providing the carboxylic acid (IX). Finally, this compound is deprotected with TFA in dichloromethane. The intermediate, the hydrazone derivative (IV) has been obtained by condensation of 2-ethylbutyryl hydrazide (X) with 3-bromo-2-oxobutyric acid ethyl ester in ethyl ether catalyzed by acetic acid.
| 【1】 Graves, B.J.; Zhang, L.; Escarpe, P.A.; Mendel, D.B.; Wang, K.-Y.; Chen, X.; Kim, C.U.; Williams, M.A.; Lawton, G.; Synthesis and evaluation of 1,4,5,6-tetrahydropyridazine derivatives as influenza neuraminidase inhibitors. Bioorg Med Chem Lett 1999, 9, 13, 1751. |
| 【2】 Zhang, L.; et al.; Synthesis and evaluation odf tetrahydropyridazine derivatives as influenza neuraminidase inhibitors. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 183. |
| 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) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (II) | 31874 | tert-butyl (Z)-2-(acetamido)ethenylcarbamate | C9H16N2O3 | 详情 | 详情 | |
| (III) | 31881 | tert-butyl (E)-2-(acetamido)ethenylcarbamate | C9H16N2O3 | 详情 | 详情 | |
| (IV) | 31875 | ethyl 3-bromo-2-[(Z)-2-(2-ethylbutanoyl)hydrazono]propanoate | C11H19BrN2O3 | 详情 | 详情 | |
| (V) | 31877 | ethyl (5S,6S)-6-(acetamido)-5-[(tert-butoxycarbonyl)amino]-1-(2-ethylbutanoyl)-1,4,5,6-tetrahydro-3-pyridazinecarboxylate | C20H34N4O6 | 详情 | 详情 | |
| (VI) | 31878 | ethyl (5S,6S)-6-(acetamido)-5-amino-1-(2-ethylbutanoyl)-1,4,5,6-tetrahydro-3-pyridazinecarboxylate | C15H26N4O4 | 详情 | 详情 | |
| (VII) | 21843 | tert-butyl [(tert-butoxycarbonyl)amino]carbothioylcarbamate | 145013-05-4 | C11H20N2O4S | 详情 | 详情 |
| (VIII) | 31879 | ethyl (5S,6S)-6-(acetamido)-5-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)-1-(2-ethylbutanoyl)-1,4,5,6-tetrahydro-3-pyridazinecarboxylate | C26H44N6O8 | 详情 | 详情 | |
| (IX) | 31880 | (5S,6S)-6-(acetamido)-5-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)-1-(2-ethylbutanoyl)-1,4,5,6-tetrahydro-3-pyridazinecarboxylic acid | C24H40N6O8 | 详情 | 详情 | |
| (X) | 31876 | 2-ethylbutanohydrazide | C6H14N2O | 详情 | 详情 | |
| (XI) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |