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【结 构 式】 
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【分子编号】58728 【品名】N,N,N-tributyl-1-butanaminium (2R,3S)-3-({2-[2-(formylamino)-1,3-thiazol-4-yl]-2-oxoacetyl}amino)-2-methyl-4-oxo-1-azetidinesulfonate 【CA登记号】 |
【 分 子 式 】C26H45N5O7S2 【 分 子 量 】603.8048 【元素组成】C 51.72% H 7.51% N 11.6% O 18.55% S 10.62% |
合成路线1
该中间体在本合成路线中的序号：(XIII)2-Formamido-4-thiazolecarboxylic acid (X) was activated as the mixed anhydride (XI) upon treatment with pivaloyl chloride and triethylamine. Subsequent coupling of anhydride (XI) with the aminoazetidinesulfonic acid (XII) provided the corresponding amide, which was further converted to the tetrabutylammonium sulfamate salt (XIII). The condensation between the keto group of (XIII) and hydroxylamine (IX) gave rise to the corresponding oxime (XIV). Finally, acid hydrolysis of the N-formyl group of (XIV) furnished the title compound.
| 【1】 Koster, W.H.; Sundeen, J.E.; Straub, H.; Ermann, P.H.; Treuner, U. (Bristol-Myers Squibb Co.); Heteroaroyl derivs. of monocyclic beta-lactam antibiotics. EP 0484881; JP 1992283579 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 58725 | 3-[(aminooxy)methyl]-6,7-dihydroxy-2-quinoxalinecarboxylic acid | C10H9N3O5 | 详情 | 详情 | |
| (X) | 31132 | 2-[2-(formylamino)-1,3-thiazol-4-yl]-2-oxoacetic acid | C6H4N2O4S | 详情 | 详情 | |
| (XI) | 58726 | 1,1-dimethylpropanoic [2-(formylamino)-1,3-thiazol-4-yl](oxo)acetic anhydride | C11H12N2O5S | 详情 | 详情 | |
| (XII) | 58727 | (2R,3S)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid | C4H8N2O4S | 详情 | 详情 | |
| (XIII) | 58728 | N,N,N-tributyl-1-butanaminium (2R,3S)-3-({2-[2-(formylamino)-1,3-thiazol-4-yl]-2-oxoacetyl}amino)-2-methyl-4-oxo-1-azetidinesulfonate | C26H45N5O7S2 | 详情 | 详情 | |
| (XIV) | 58729 | disodium 3-({[((Z)-1-[2-(formylamino)-1,3-thiazol-4-yl]-2-{[(2R,3S)-2-methyl-4-oxo-1-sulfonatoazetidinyl]amino}-2-oxoethylidene)amino]oxy}methyl)-6,7-dihydroxy-2-quinoxalinecarboxylate | C20H15N7Na2O11S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)In an alternative route to the title compound, dinitro derivative (XV) was converted into the benzofuroxan (XVI) by treatment with sodium azide in hot DMSO. Furazan ring opening by means of tert-butyl acetoacetate (XVII) under basic conditions generated the quinoxaline N,N'-dioxide (XVIII). The Pummerer-like rearrangement of the N-oxide (XVIII) in the presence of trifluoroacetic anhydride gave rise to the unstable trifluoroacetoxymethyl quinoxaline (XIX), which was further converted to bromide (XX) upon heating with LiBr in acetone. Alkylation of N,N-di-Boc-hydroxylamine (III) with bromide (XX) provided the protected O-alkyl hydroxylamine (XXI). Reduction of the remaining N-oxide group of (XXI) and simultaneous N-Boc groups cleavage by means of boron tribromide furnished quinoxaline (XXII). The fully deprotected quinoxaline (IX) was then obtained by acidic treatment of (XXII). Condensation of keto amide (XIII) with hydroxylamine (IX) in the presence of tetrabutylammonium bisulfate produced the oxime adduct (XXIII). Finally, the title compound was obtained by deformylation of (XXIII) under acidic conditions.
| 【1】 Koster, W.H.; Sundeen, J.E.; Straub, H.; Ermann, P.H.; Treuner, U. (Bristol-Myers Squibb Co.); Heteroaroyl derivs. of monocyclic beta-lactam antibiotics. EP 0484881; JP 1992283579 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 58719 | 2-({[(tert-butoxycarbonyl)(hydroxy)amino]carbonyl}oxy)-2-methylpropane | C10H19NO5 | 详情 | 详情 | |
| (IX) | 58725 | 3-[(aminooxy)methyl]-6,7-dihydroxy-2-quinoxalinecarboxylic acid | C10H9N3O5 | 详情 | 详情 | |
| (XIII) | 58728 | N,N,N-tributyl-1-butanaminium (2R,3S)-3-({2-[2-(formylamino)-1,3-thiazol-4-yl]-2-oxoacetyl}amino)-2-methyl-4-oxo-1-azetidinesulfonate | C26H45N5O7S2 | 详情 | 详情 | |
| (XV) | 58730 | 2,2-dimethyl-5,6-dinitro-1,3-benzodioxole | C9H8N2O6 | 详情 | 详情 | |
| (XVI) | 58731 | 6,6-dimethyl[1,3]dioxolo[4,5-f][2,1,3]benzoxadiazol-1-ium-1-olate | C9H8N2O4 | 详情 | 详情 | |
| (XVII) | 27907 | Acetoacetic acid tert-butyl ester;3-Oxo-butanoic acid 1,1-dimethylethyl estertert-butyl 3-oxobutanoate | 1694-31-1 | C8H14O3 | 详情 | 详情 |
| (XVIII) | 58732 | 6-(tert-butoxycarbonyl)-2,2,7-trimethyl[1,3]dioxolo[4,5-g]quinoxaline-5,8-diium-5,8-diolate | C17H20N2O6 | 详情 | 详情 | |
| (XIX) | 58733 | 6-(tert-butoxycarbonyl)-2,2-dimethyl-7-{[(2,2,2-trifluoroacetyl)oxy]methyl}[1,3]dioxolo[4,5-g]quinoxalin-5-ium-5-olate | C19H19F3N2O7 | 详情 | 详情 | |
| (XX) | 58734 | 7-(bromomethyl)-6-(tert-butoxycarbonyl)-2,2-dimethyl[1,3]dioxolo[4,5-g]quinoxalin-5-ium-5-olate | C17H19BrN2O5 | 详情 | 详情 | |
| (XXI) | 58735 | 7-({[bis(tert-butoxycarbonyl)amino]oxy}methyl)-6-(tert-butoxycarbonyl)-2,2-dimethyl[1,3]dioxolo[4,5-g]quinoxalin-5-ium-5-olate | C27H37N3O10 | 详情 | 详情 | |
| (XXII) | 58736 | tert-butyl 7-[(aminooxy)methyl]-2,2-dimethyl[1,3]dioxolo[4,5-g]quinoxaline-6-carboxylate | C17H21N3O5 | 详情 | 详情 | |
| (XXIII) | 58737 | di(N,N,N-tributyl-1-butanaminium) 3-({[((Z)-1-[2-(formylamino)-1,3-thiazol-4-yl]-2-{[(2R,3S)-2-methyl-4-oxo-1-sulfonatoazetidinyl]amino}-2-oxoethylidene)amino]oxy}methyl)-6,7-dihydroxy-2-quinoxalinecarboxylate | C52H87N9O11S2 | 详情 | 详情 |