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【结 构 式】 
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【分子编号】32981 【品名】methyl 4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzenecarbodithioate 【CA登记号】 |
【 分 子 式 】C14H15FN2O3S2 【 分 子 量 】342.4151832 【元素组成】C 49.11% H 4.42% F 5.55% N 8.18% O 14.02% S 18.73% |
合成路线1
该中间体在本合成路线中的序号：(V)Diazotization of the known aniline (I), followed by Sandmeyer reaction with CuCN and KCN afforded nitrile (II). Addition of hydrogen sulfide to (II) in the presence of Et3N in hot DMF led to the thioamide (III). Subsequent alkylation of (III) with methyl triflate gave the intermediate thioimidate (IV), and a further treatment of (IV) with hydrogen sulfide and pyridine provided dithioester (V). Displacement of the methylthio group of (V) by hydrazine yielded thiohydrazide (VI). Finally, cyclization of (VI) to the target thiadiazole was achieved upon refluxing in formic acid.
| 【1】 Ford, C.W.; Gadwood, R.C.; Thomasco, L.M.; Weaver, E.A.Zurenko, G.E.; Synthesis and antibacterial activity of azolylphenyl oxazolidinones having 1,3,4-thiadiazolyl C-rings. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F571. |
| 【2】 Gadwood, R.C.; Thomasco, L.M.; Anderson, D.J. (Pharmacia Corp.); Thiadiazolyl and oxadiazolyl phenyl oxazolidinone antibacterial agents. EP 0994874; WO 9902525 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 27344 | hydrazine | 302-01-2 | H4N2 | 详情 | 详情 | |
| (I) | 28504 | N-[[(5S)-3-(4-amino-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide | C12H14FN3O3 | 详情 | 详情 | |
| (II) | 28555 | N-[[(5S)-3-(4-cyano-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide | C13H12FN3O3 | 详情 | 详情 | |
| (III) | 28556 | N-([(5S)-3-[4-(aminocarbothioyl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)acetamide | C13H14FN3O3S | 详情 | 详情 | |
| (IV) | 32980 | methyl 4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzenecarbimidothioate | C14H16FN3O3S | 详情 | 详情 | |
| (V) | 32981 | methyl 4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzenecarbodithioate | C14H15FN2O3S2 | 详情 | 详情 | |
| (VI) | 32982 | N-([(5S)-3-[3-fluoro-4-(hydrazinocarbothioyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)acetamide | C13H15FN4O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Diazotization of the known aniline (I), followed by Sandmeyer reaction with CuCN and KCN afforded nitrile (II). Addition of hydrogen sulfide to (II) in the presence of Et3N in hot DMF led to the thioamide (III). Subsequent alkylation of (III) with methyl triflate gave the intermediate thioimidate (IV), and a further treatment of (IV) with hydrogen sulfide and pyridine provided dithioester (V). Displacement of the methylthio group of (V) by hydrazine yielded thiohydrazide (VI). This was cyclized to the required thiadiazole (VII) upon treatment with 3-carbomethoxypropionyl chloride (A) in refluxing THF. Aminolysis of the ester group of (VII) with methanolic ammonia at 100 C in a sealed vessel provided amide (VIII). This was finally dehydrated to the title nitrile using trifluoroacetic anhydride and pyridine.
| 【1】 Ford, C.W.; Gadwood, R.C.; Thomasco, L.M.; Weaver, E.A.Zurenko, G.E.; Synthesis and antibacterial activity of azolylphenyl oxazolidinones having 1,3,4-thiadiazolyl C-rings. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F571. |
| 【2】 Gadwood, R.C.; Thomasco, L.M.; Anderson, D.J. (Pharmacia Corp.); Thiadiazolyl and oxadiazolyl phenyl oxazolidinone antibacterial agents. EP 0994874; WO 9902525 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 27344 | hydrazine | 302-01-2 | H4N2 | 详情 | 详情 | |
| (A) | 18060 | 4-Chloro-4-oxobutyric acid methyl ester; 3-Carbomethosypropionyl chloride; Methyl 4-chloro-4-oxobutanoate | 1490-25-1 | C5H7ClO3 | 详情 | 详情 |
| (I) | 28504 | N-[[(5S)-3-(4-amino-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide | C12H14FN3O3 | 详情 | 详情 | |
| (II) | 28555 | N-[[(5S)-3-(4-cyano-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide | C13H12FN3O3 | 详情 | 详情 | |
| (III) | 28556 | N-([(5S)-3-[4-(aminocarbothioyl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)acetamide | C13H14FN3O3S | 详情 | 详情 | |
| (IV) | 32980 | methyl 4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzenecarbimidothioate | C14H16FN3O3S | 详情 | 详情 | |
| (V) | 32981 | methyl 4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorobenzenecarbodithioate | C14H15FN2O3S2 | 详情 | 详情 | |
| (VI) | 32982 | N-([(5S)-3-[3-fluoro-4-(hydrazinocarbothioyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl)acetamide | C13H15FN4O3S | 详情 | 详情 | |
| (VII) | 32983 | methyl 3-[5-(4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1,3,4-thiadiazol-2-yl]propanoate | C18H19FN4O5S | 详情 | 详情 | |
| (VIII) | 32984 | 3-[5-(4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1,3,4-thiadiazol-2-yl]propanamide | C17H18FN5O4S | 详情 | 详情 |