(3R)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-N-methyl-3-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanamide -Drug Synthesis Database

【结构式】

【分子编号】32626

【品名】(3R)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-N-methyl-3-[[(2-nitrophenyl)sulfonyl]amino]-4-oxobutanamide

【CA登记号】

【分子式】C₁₅H₁₆N₄O₉S

【分子量】428.3796

【元素组成】C 42.06% H 3.76% N 13.08% O 33.61% S 7.49%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

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.

参考文献中间体

合成目标

【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

Extended Information