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【结 构 式】 
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【分子编号】45484 【品名】benzhydryl (6R,7R)-7-amino-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C21H20N2O6S2 【 分 子 量 】460.53168 【元素组成】C 54.77% H 4.38% N 6.08% O 20.84% S 13.93% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Thiadiazole (II) was synthesized from 3-aminoisoxazole (I) following a known procedure. Esterification of (II) to give (III) was carried out by treatment with MeOH and SOCl2. Subsequent oxidation of (III) employing I2 in DMSO provided keto ester (IV), which was converted into oxime (V) and then protected as the O-trityl derivative (VI). Basic hydrolysis of the methyl ester group yielded carboxylic acid (VII). Then, coupling of acid (VII) with aminocephalosporin (VIII) by means of POCl3 furnished the corresponding amide (IX).
| 【1】 Griffith, D.; Blais, J.; Hevker, S.; Price, M.; Huie, K.; Halas, S.; Cho, A.; Dudley, M.; Lee, V.; Ludwikow, M.; Chen, S.; Chemberland, S.; Glinka, T.; Discovery of novel anti-MRSA cephalosporin RWJ-333441 (MC-04,546). Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in a series of (3-heteroarylthio)cephems. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1071. |
| 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) | 45477 | 3-isoxazolylamine; 3-isoxazolamine | 1750-42-1 | C3H4N2O | 详情 | 详情 |
| (II) | 45478 | 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetic acid | C6H7N3O4S | 详情 | 详情 | |
| (III) | 45479 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetate | C7H9N3O4S | 详情 | 详情 | |
| (IV) | 45480 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-oxoacetate | C7H7N3O5S | 详情 | 详情 | |
| (V) | 45481 | methyl 2-(hydroxyimino)-2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetate | C7H8N4O5S | 详情 | 详情 | |
| (VI) | 45482 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetate | C26H22N4O5S | 详情 | 详情 | |
| (VII) | 45483 | 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetic acid | C25H20N4O5S | 详情 | 详情 | |
| (VIII) | 45484 | benzhydryl (6R,7R)-7-amino-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H20N2O6S2 | 详情 | 详情 | |
| (IX) | 45485 | benzhydryl (6R,7R)-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C46H38N6O10S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Thiadiazole (II) was synthesized from 3-aminoisoxazole (I) following a known procedure. Esterification of (II) to give (III) was carried out by treatment with MeOH and SOCl2. Subsequent oxidation of (III) employing I2 in DMSO provided keto ester (IV), which was converted into oxime (V) and then protected as the O-trityl derivative (VI). Basic hydrolysis of the methyl ester group yielded carboxylic acid (VII). Then, coupling of acid (VII) with aminocephalosporin (VIII) by means of POCl3 furnished the corresponding amide (IX).
| 【1】 Griffith, D.; Blais, J.; Hevker, S.; Price, M.; Huie, K.; Halas, S.; Cho, A.; Dudley, M.; Lee, V.; Ludwikow, M.; Chen, S.; Chemberland, S.; Glinka, T.; Discovery of novel anti-MRSA cephalosporin RWJ-333441 (MC-04,546). Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in a series of (3-heteroarylthio)cephems. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1071. |
| 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) | 45477 | 3-isoxazolylamine; 3-isoxazolamine | 1750-42-1 | C3H4N2O | 详情 | 详情 |
| (II) | 45478 | 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetic acid | C6H7N3O4S | 详情 | 详情 | |
| (III) | 45479 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetate | C7H9N3O4S | 详情 | 详情 | |
| (IV) | 45480 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-oxoacetate | C7H7N3O5S | 详情 | 详情 | |
| (V) | 45481 | methyl 2-(hydroxyimino)-2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]acetate | C7H8N4O5S | 详情 | 详情 | |
| (VI) | 45482 | methyl 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetate | C26H22N4O5S | 详情 | 详情 | |
| (VII) | 45483 | 2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetic acid | C25H20N4O5S | 详情 | 详情 | |
| (VIII) | 45484 | benzhydryl (6R,7R)-7-amino-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C21H20N2O6S2 | 详情 | 详情 | |
| (IX) | 45485 | benzhydryl (6R,7R)-7-([2-[5-[(methoxycarbonyl)amino]-1,2,4-thiadiazol-3-yl]-2-[(trityloxy)imino]acetyl]amino)-3-[(methylsulfonyl)oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C46H38N6O10S3 | 详情 | 详情 |