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【结 构 式】 
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【分子编号】19844 【品名】benzhydryl (6S,7S)-7-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-methyl-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C29H22N2O5S 【 分 子 量 】510.57016 【元素组成】C 68.22% H 4.34% N 5.49% O 15.67% S 6.28% |
合成路线1
该中间体在本合成路线中的序号：(V)The D-threonine (I) is converted into the azetidinone (II), and into the enol (III) according to (Tsubouchi, H., et al. Tetrahedron Assimetry, 1944, 5: 441). The tosylation of (III) with tosyl chloride and N-methylpyrrolidine yielded the tosylated enol (IV), which was cyclized with H2S and triethylamine to the isocephem derivative (V). The chlorination of (V) with N-bromosuccinimide (NBS) and AIBN affords the bromomethyl derivative (VI), which is treated with 2-(4-methyl-2-sulfanylthiazol-5-yl)acetic acid (VII) and triethylamine or NaHCO3 and then esterified with diphenyldiazomethane to give the expected condensation product (VIII). The reaction of (VIII) with methylhydrazine cleaves the phthalimide group affording (IX), which is then amidated wih the acetic acid derivative (X) by means of dicyclohexylcarbodiimide (DCC) givig the fully protected final product (XI). Finally, this compound is treated with trifluoroacetic acid to eliminate the diphenyl nad triphenyl protecting groups.
| 【1】 Tsuji, K.; et al.; Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics. Bioorg Med Chem 1996, 4, 12, 2135. |
| 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) | 19840 | (2R,3S)-3-hydroxy-2-methylbutyric acid | C5H10O3 | 详情 | 详情 | |
| (II) | 19841 | benzhydryl (2R,3S)-2-[(3S,4R)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-oxo-4-[(E)-2-phenylethenyl]azetidinyl]-3-hydroxybutanoate | C36H30N2O6 | 详情 | 详情 | |
| (III) | 19842 | benzhydryl (Z)-2-((2R,3S)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4-oxoazetidinyl)-3-hydroxy-2-butenoate | C31H28N2O7S | 详情 | 详情 | |
| (IV) | 19843 | benzhydryl (Z)-2-((2R,3S)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4-oxoazetidinyl)-3-[[(4-methylphenyl)sulfonyl]oxy]-2-butenoate | C38H34N2O9S2 | 详情 | 详情 | |
| (V) | 19844 | benzhydryl (6S,7S)-7-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-methyl-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H22N2O5S | 详情 | 详情 | |
| (VI) | 19845 | benzhydryl (6S,7S)-3-(bromomethyl)-7-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C29H21BrN2O5S | 详情 | 详情 | |
| (VII) | 19846 | 2-(4-methyl-2-sulfanyl-1,3-thiazol-5-yl)acetic acid | 34272-64-5 | C6H7NO2S2 | 详情 | 详情 |
| (VIII) | 19847 | benzhydryl (6S,7S)-3-[([5-[2-(benzhydryloxy)-2-oxoethyl]-4-methyl-1,3-thiazol-2-yl]sulfanyl)methyl]-7-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C48H37N3O7S3 | 详情 | 详情 | |
| (IX) | 19848 | benzhydryl (6S,7S)-7-amino-3-[([5-[2-(benzhydryloxy)-2-oxoethyl]-4-methyl-1,3-thiazol-2-yl]sulfanyl)methyl]-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C40H35N3O5S3 | 详情 | 详情 | |
| (X) | 19849 | 2-([[1,5-bis(benzhydryloxy)-4-oxo-1,4-dihydro-2-pyridinyl]methoxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid | C56H44N4O6S | 详情 | 详情 | |
| (XI) | 19850 | benzhydryl (6S,7S)-3-[([5-[2-(benzhydryloxy)-2-oxoethyl]-4-methyl-1,3-thiazol-2-yl]sulfanyl)methyl]-7-([2-([[1,5-bis(benzhydryloxy)-4-oxo-1,4-dihydro-2-pyridinyl]methoxy]imino)-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino)-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C96H77N7O10S4 | 详情 | 详情 |