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【结 构 式】 
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【分子编号】15705 【品名】1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-[[4-bromo-2-(hydroxyimino)-3-oxobutanoyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C21H27BrN4O11S 【 分 子 量 】623.43574 【元素组成】C 40.46% H 4.37% Br 12.82% N 8.99% O 28.23% S 5.14% |
合成路线1
该中间体在本合成路线中的序号：(IVb)The synthesis of [14C]-labeled E-1101 has been reported: (6R,7R)-7-Amino-3-(N,N-dimethylcarbamoyloxymethyl)-3-cephem-4-carboxyli c acid 1-(isopropoxycarbonyloxy)ethyl ester (I) is a diastereomeric mixture (Ia and Ib) due to the asymmetric carbon in the ester group. These isomers are separated by crystallization in THF and submitted separately to the following reaction sequence: The reaction of (Ia) and (Ib) with diketene (II) and Br2 gives the 4-bromo-3-oxobutyrylamides (IIIa and IIIb), which by oxidation with acetyl chloride and butylnitrite in dichloromethane yield the hydroxyimino derivatives (IVa and IVb). The cyclization of (IVa) and (IVb) with [14C]-labeled thiourea (V) in dimethylacetamide affords the two labeled diastereomeric E-1101 compounds (VIa and VIb), which are finally mixed equimolecularly to obtain the labeled E-1101 racemic at the ester group.
| 【1】 Uemura, Y.; Komatsu, Y.; Negi, S.; Tsuruoka, A.; Synthesis of a radiolabelled new oral cephalosporin, E1101. J Label Compd Radiopharm 1996, 38, 1, 1. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Ia) | 15699 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7R)-7-amino-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C17H25N3O8S | 详情 | 详情 | |
| (Ib) | 15700 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-amino-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C17H25N3O8S | 详情 | 详情 | |
| (IIIa) | 15702 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7R)-7-[(4-bromo-3-oxobutanoyl)amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H28BrN3O10S | 详情 | 详情 | |
| (IIIb) | 15703 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-[(4-bromo-3-oxobutanoyl)amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H28BrN3O10S | 详情 | 详情 | |
| (IVa) | 15704 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7R)-7-[[4-bromo-2-(hydroxyimino)-3-oxobutanoyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H27BrN4O11S | 详情 | 详情 | |
| (IVb) | 15705 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-[[4-bromo-2-(hydroxyimino)-3-oxobutanoyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H27BrN4O11S | 详情 | 详情 | |
| (VIa) | 15707 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H28N6O10S2 | 详情 | 详情 | |
| (VIb) | 15708 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H28N6O10S2 | 详情 | 详情 | |
| (VIa) | 45262 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H28N6O10S2 | 详情 | 详情 | |
| (VIb) | 45263 | 1-[(isopropoxycarbonyl)oxy]ethyl (6R,7S)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(hydroxyimino)acetyl]amino]-3-([[(dimethylamino)carbonyl]oxy]methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C22H28N6O10S2 | 详情 | 详情 | |
| (II) | 15701 | 2,4-oxetanedione | C3H2O3 | 详情 | 详情 | |
| (V) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |