4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid -Drug Synthesis Database

【结构式】

【分子编号】16296

【品名】4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid

【CA登记号】

【分子式】C₁₁H₁₃N₃O₃

【分子量】235.24264

【元素组成】C 56.16% H 5.57% N 17.86% O 20.4%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 4-aminobenzamidine dihydrochloride (I) with succinic anhydride and pyridine in hot DMF gives the succinyl derivative (II), which is activated with isobutyl chloroformate and N-methylmorpholine (NMM) and then coupled to 3(S)-amino-4-pentynoic acid ethyl ester (III) in DMF or DMAc.

参考文献中间体

合成目标

【1】 Zablocki, J.A.; Rico, J.G.; Garland, R.B.; et al.; Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp sequence of fibrinogen. (Aminobenzamidino)succinyl (ABAS) series of orally active fibrinogen receptor antagonists. J Med Chem 1995, 38, 13, 2378-94.
【2】 Graul, A.; Martel, A.M.; Castaner, J.; Xemilofiban. Drugs Fut 1997, 22, 5, 508.
【3】 Bovy, P.R.; Rico, J.G.; Rogers, T.E.; Tjoeng, F.S.; Zablocki, J.A. (Pharmacia Corp.); Substd. beta-amino acid derivs. useful as platelet aggregation inhibitors. EP 0542708; EP 0614360; JP 1995500111; US 5239113; WO 9307867 .
【4】 Process for the preparation of ethyl 3S-[4[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate. US 5536869 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11291	Dihydro-2,5-furandione; Succinic anhydride	108-30-5	C₄H₄O₃	详情	详情
(I)	16295	4-aminobenzenecarboximidamide hydrochloride; 4-aminobenzamidine	3858-83-1	C₇H₉N₃	详情	详情
(II)	16296	4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid		C₁₁H₁₃N₃O₃	详情	详情
(III)	16297	ethyl (3S)-3-amino-4-pentynoate		C₇H₁₁NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

A short and efficient synthesis of xemilofiban has been achieved as follows: The reaction of ethyl chloroformate (I) with trimethylsilylacetylene (II) by means of butyllithium gives ethyl 3-(trimethylsilyl)propyonate (III), which is condensed with the lithium salt of ethyl acetate (IV) yielding ethyl 5-(trimethylsilyl)-3-oxo-4-pentynoate (V). The selective reduction of (V) with lyophilized baker's yeast (Saccharomyces cerevisiae, Sigma type II) affords ethyl 3(R)-hydroxy-5-(trimethylsilyl)-4-pentynoate (VI), which by reaction with ammonia (VII), diethyl azodicarboxylate (VIII) and triphenylphosphine, followed by hydrolysis with water gives 3(S)-amino-5-(trimethylsilyl)-4-pentynoate (IX). Finally, this compound is condensed with N-(4-amidinophenyl)succinamic acid (XI) by means of isobutyl chloroformate and N-methylmorpholine (NMM). The intermediate succinamic acid (XI) has been obtained by condensation of 4-aminobenzamidine (XII) with succinic anhydride (XIII) in DMF.

参考文献中间体

合成目标

【1】 Cossy, J.; Schmitt, A.; Cinquin, C.; Buisson, D.; Belotti, D.; A very short, efficient and inexpensive synthesis of the prodrug form of SC-54701A a platelet aggregation inhibitor. Bioorg Med Chem Lett 1997, 7, 13, 1699.

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)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(II)	23897	ethynyl(trimethyl)silane；trimethylsilyl acetylene	1066-54-2	C₅H₁₀Si	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	23899	lithium 1-ethoxy-1-ethylenolate		C₄H₇LiO₂	详情	详情
(V)	23900	ethyl 3-oxo-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₆O₃Si	详情	详情
(VI)	23901	ethyl (3R)-3-hydroxy-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₈O₃Si	详情	详情
(VIII)	20989	Diethylazadicarboxylate; Diethyl Azodiformate; Azodiformic Acid Diethyl Ester; Diethyl Azodicarboxylate; Azodicarboxylic Acid Diethyl Ester; Diethyl 1,2-diazenedicarboxylate	1972-28-7	C₆H₁₀N₂O₄	详情	详情
(IX)	23904	ethyl (3S)-3-amino-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₉NO₂Si	详情	详情
(X)	16297	ethyl (3S)-3-amino-4-pentynoate		C₇H₁₁NO₂	详情	详情
(XI)	16296	4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid		C₁₁H₁₃N₃O₃	详情	详情
(XII)	16295	4-aminobenzenecarboximidamide hydrochloride; 4-aminobenzamidine	3858-83-1	C₇H₉N₃	详情	详情
(XIII)	11291	Dihydro-2,5-furandione; Succinic anhydride	108-30-5	C₄H₄O₃	详情	详情

Extended Information