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【结 构 式】 
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【分子编号】13222 【品名】6-[(4-Methoxybenzyl)sulfanyl]-5H,6H,7H-pyrazolo[1,2-a][1,2,4]triazol-4-ium chloride 【CA登记号】 |
【 分 子 式 】C13H16ClN3OS 【 分 子 量 】297.80836 【元素组成】C 52.43% H 5.42% Cl 11.9% N 14.11% O 5.37% S 10.77% |
合成路线1
该中间体在本合成路线中的序号：(X)2) The acylation of hydrazine (I) with di-tert-butyl dicarbonate (II) gives 1,2-di(tert-butyloxycarbonyl)hydrazine (III), which is cyclized with 1,3-dibromo-2-(tert-butyldimethylsilyloxy)propane (IV) by means of NaH in DMF yielding the pyrazolidine (V). The desilylation of (V) with tetrabutylammonium fluoride in THF affords 1,2-di(tert-butoxycarbonyl)-4-hydroxypyrazolidine (VI). Acylation of (VI) with methanesulfonyl chloride in dichloromethane gives the corresponding mesylate (VII), which is condensed with 4-methoxybenzyl mercaptane (VIII) by means of butyllithium in hexane to yield the benzyl ether (IX). The cyclization of (IX) with methyl formimidate hydrochloride in methanol-water affords 6-(4-methoxybenzylthio)-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium chloride (X), which is deprotected with trifluoroacetic acid giving 6-mercapto-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium chloride (XI). Finally, this compound is condensed with (1R,5R,6S)-2-(diphenylphosphonooxy)-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid 4-nitrobenzyl ester (XII) by means of diisopropylethylamine in DMF followed by hydrogenolysis with H2 over Pd/C in butanol-EtOAc-potassium phosphate buffer.
| 【1】 Ratcliffe, R.W.; Wildonger, K.J.; Heteroaryliumthio substituted carbapenem derivatives: Synthesis and in vitro activity of 1beta-methyl-2-(dihydropyrrolotriazoliumthio)carbapenems. J Antibiot 1993, 46, 12, 1866-82. |
| 【2】 Rabasseda, X.; Prous, J.; Castaner, J.; Biapenem. Drugs Fut 1994, 19, 7, 631. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 13214 | Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate | 24424-99-5 | C10H18O5 | 详情 | 详情 |
| (III) | 13215 | di(tert-butyl) 1,2-hydrazinedicarboxylate; Di-tert-butyl hydrazodicarboxylate | 16466-61-8 | C10H20N2O4 | 详情 | 详情 |
| (IV) | 13216 | [2-Bromo-1-(bromomethyl)ethoxy](tert-butyl)dimethylsilane; 2-Bromo-1-(bromomethyl)ethyl tert-butyl(dimethyl)silyl ether | C9H20Br2OSi | 详情 | 详情 | |
| (V) | 13217 | di(tert-butyl) 4-[[tert-butyl(dimethyl)silyl]oxy]-1,2-pyrazolidinedicarboxylate | C19H38N2O5Si | 详情 | 详情 | |
| (VI) | 13218 | di(tert-butyl) 4-hydroxy-1,2-pyrazolidinedicarboxylate | C13H24N2O5 | 详情 | 详情 | |
| (VII) | 13219 | di(tert-butyl) 4-[(methylsulfonyl)oxy]-1,2-pyrazolidinedicarboxylate | C14H26N2O7S | 详情 | 详情 | |
| (VIII) | 13220 | 4-Methoxybenzylhydrosulfide; (4-Methoxyphenyl)methanethiol; 4-Methoxy-alpha-toluenethiol | 6258-60-2 | C8H10OS | 详情 | 详情 |
| (IX) | 13221 | di(tert-butyl) 4-[(4-methoxybenzyl)sulfanyl]-1,2-pyrazolidinedicarboxylate | C21H32N2O5S | 详情 | 详情 | |
| (X) | 13222 | 6-[(4-Methoxybenzyl)sulfanyl]-5H,6H,7H-pyrazolo[1,2-a][1,2,4]triazol-4-ium chloride | C13H16ClN3OS | 详情 | 详情 | |
| (XI) | 13223 | 6-Sulfanyl-5H,6H,7H-pyrazolo[1,2-a][1,2,4]triazol-4-ium chloride | 153851-71-9 | C5H8ClN3S | 详情 | 详情 |
| (XII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |