|
【结 构 式】 
|
【分子编号】32628 【品名】(2S,5R,6R)-6-([(2R)-2-(4-hydroxyphenyl)-2-[((2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanoyl)amino]ethanoyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid 【CA登记号】 |
【 分 子 式 】C27H30N6O11S2 【 分 子 量 】678.70104 【元素组成】C 47.78% H 4.46% N 12.38% O 25.93% S 9.45% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 2-amino-3-(N-methylcarbamoyl)propionic acid (I) with 2-nitrophenylsulfonylchloride (II) by means of K2CO3 in THF gives 2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionic acid (III), which is esterified with N-hydroxysuccinimide (IV) by means of dicyclohexylcarbodiimide in THF yielding the corresponding N-succinimido ester (V). The condensation of (V) with amoxicillin [6-[alpha-amino-alpha-(4-hydroxyphenyl)acetylamino]penicillanic acid] (VI) by means of triethylamine in THF-CHCl3 affords 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid (VII). Finally, the sulfonic group is eliminated by treatment with thiobenzamide (A) in ethanol-THF.
| 【1】 Kawazu, M.; et al. (Tanabe Seiyaku Co., Ltd.); Penicillins and processes for preparing the same. DE 2638067; FR 2323384; NL 7610151; US 4053609 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; TA-058. Drugs Fut 1980, 5, 3, 151. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 32629 | Thiobenzamide; Benzenecarbothioamide | 2227-79-4 | C7H7NS | 详情 | 详情 |
| (I) | 32623 | (2R)-2-amino-3-(N-methylcarbamoyl)propionic acid; (2R)-2-amino-4-(methylamino)-4-oxobutyric acid | C5H10N2O3 | 详情 | 详情 | |
| (II) | 32624 | 2-Nitrobenzenesulfonyl chloride | 1694-92-4 | C6H4ClNO4S | 详情 | 详情 |
| (III) | 32625 | (2R)-2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionic acid; (2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutyric acid | C11H13N3O7S | 详情 | 详情 | |
| (IV) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |
| (V) | 32626 | (3R)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-N-methyl-3-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanamide | C15H16N4O9S | 详情 | 详情 | |
| (VI) | 32627 | 6-[alpha-amino-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid; Amoxicillin; (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)ethanoyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid | 26787-78-0 | C16H19N3O5S | 详情 | 详情 |
| (VII) | 32628 | (2S,5R,6R)-6-([(2R)-2-(4-hydroxyphenyl)-2-[((2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanoyl)amino]ethanoyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid | C27H30N6O11S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Compound (VII) can also be obtained by condensation of 6-aminopenicillanic acid (VIII) with the N-succinimido ester of alpha-[2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionamido]-alpha-(4-hydroxyphenyl)acetic acid (IX). Finally, the sulfonic group of (VII) is eliminated by treatment with thiobenzamide (A) in ethanol-THF.
| 【1】 Kawazu, M.; et al. (Tanabe Seiyaku Co., Ltd.); Penicillins and processes for preparing the same. DE 2638067; FR 2323384; NL 7610151; US 4053609 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; TA-058. Drugs Fut 1980, 5, 3, 151. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 32629 | Thiobenzamide; Benzenecarbothioamide | 2227-79-4 | C7H7NS | 详情 | 详情 |
| (VII) | 32628 | (2S,5R,6R)-6-([(2R)-2-(4-hydroxyphenyl)-2-[((2R)-4-(methylamino)-2-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanoyl)amino]ethanoyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid | C27H30N6O11S2 | 详情 | 详情 | |
| (VIII) | 32631 | (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (+)-6-Aminopenicillanic acid; 6-APA | 551-16-6 | C8H12N2O3S | 详情 | 详情 |
| (IX) | 32630 | (2R)-N(1)-[(1R)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-(4-hydroxyphenyl)-2-oxoethyl]-N(4)-methyl-2-[[(2-nitrophenyl)sulfonyl]amino]butanediamide | C23H23N5O11S | 详情 | 详情 |