1-nitrosopiperazine -Drug Synthesis Database

【结构式】

【分子编号】17260

【品名】1-nitrosopiperazine

【CA登记号】

【分子式】C₄H₉N₃O

【分子量】115.13508

【元素组成】C 41.73% H 7.88% N 36.5% O 13.9%

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：(VI)

This compound has been obtained by two related ways: 1) The saponification of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid methyl ester (I) with NaOH in methanol/water gives the corresponding free acid (II), which is condensed with piperazine (III) by means of TiCl4 in THF yielding the acyl piperazine (IV). The nitrosation of (IV) with isoamyl nitrite in dichloromethane affords the N-nitrosopiperazine (V), which is finally reduced with Zn and acetic acid to the target amino derivative. 2) The nitrosation of piperazine (III) with NaNO2 and acetic acid gives 1-nitrosopiperazine (VI), which is reduced with Zn and acetic acid to 1-aminopiperazine (VII). The reaction of (VII) with benzaldehyde affords 1-(benzylideneamino)piperazine (VIII), which is condensed with of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid (II) by means of SOCl2 and triethylamine in dichloromethane yielding the acyl piperazine (IX). Finally, this compound is debenzylated with hydroxylamine and HCl in acetonitrile/water.

参考文献中间体

合成目标

【1】 Matsuo, M.; Nakaguchi, O.; Okumura, H.; Tsuji, K.; Ueda, I. (Fujisawa Pharmaceutical Co., Ltd.); N-Containing fused heterocyclic cpds., processes for the preparation thereof and pharmaceutical compsn. comprising the same. EP 0232740; JP 1987181253; US 4797399 .
【2】 Zanka, A.; et al.; Process development of a platelet aggregation inhibitor. Org Process Res Dev 1998, 2, 6, 418.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(I)	35662	methyl 2-[5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl]acetate		C₁₀H₈ClNO₃S	详情	详情
(II)	35663	2-[5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl]acetic acid		C₉H₆ClNO₃S	详情	详情
(III)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(IV)	35664	5-chloro-3-[2-oxo-2-(1-piperazinyl)ethyl]-1,3-benzothiazol-2(3H)-one		C₁₃H₁₄ClN₃O₂S	详情	详情
(V)	35665	5-chloro-3-[2-(4-nitroso-1-piperazinyl)-2-oxoethyl]-1,3-benzothiazol-2(3H)-one		C₁₃H₁₃ClN₄O₃S	详情	详情
(VI)	17260	1-nitrosopiperazine		C₄H₉N₃O	详情	详情
(VII)	35666	1-piperazinylamine; 1-piperazinamine		C₄H₁₁N₃	详情	详情
(VIII)	35667	N-[(E)-benzylidene]-N-(1-piperazinyl)amine; N-[(E)-benzylidene]-1-piperazinamine		C₁₁H₁₅N₃	详情	详情
(IX)	35668	5-chloro-3-[2-oxo-2-(4-[[(E)-benzylidene]amino]-1-piperazinyl)ethyl]-1,3-benzothiazol-2(3H)-one		C₂₀H₁₉ClN₄O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

This compound can be obtained by two different ways: 1) The acetylation of 1-nitrosopiperazine (I) with acetyl chloride and pyridine in dioxane gives 1-acetyl-4-nitrosopiperazine (II), which is reduced with Zn and acetic acid/water to 1-acetyl-4-aminopiperazine (III). Finally, this compound is acylated with 4-fluorobenzoyl chloride (IV) by means of triethylamine in dichloromethane. 2) The nitrosation of piperazine (V) with NaNO2/HCl in water, followed by condensation with benzyloxycarbonyl chloride (VI) by means of NaOH yields 1-(benzyloxycarbonyl)-4-nitrosopiperazine (VII), which is reduced with Zn and acetic acid/water as before to the corresponding amino derivative (VIII). The acylation of (VIII) with 4-fluorobenzoyl chloride and triethylamine in dichloromethane affords N-[4-(benzyloxycarbonyl)piperazin-1-yl]-4-fluorobenzamide (IX), which is deprotected with HBr in acetic acid to yield N-(1-piperazinyl)-4-fluorobenzamide (X). Finally, this compound is acetylated with acetic anhydride/NaOH in water.

参考文献中间体

合成目标

【1】 Graul, A.; Tracy, M.; Castañer, J.; FK-960. Drugs Fut 1997, 22, 8, 830.
【2】 Oku, T.; Todo, E.; Yokota, Y.; Kayakiri, H.; Hashimoto, M. (Fujisawa Pharmaceutical Co., Ltd.); New aminopiperazine derivs. EP 0436734; JP 1991510050; US 5250528; WO 9101979 .
【3】 Oku, T.; Kayakiri, H.; Tanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); Novel intermediate for synthetic use and process for producing aminopiperazine derivs. WO 9500502 .

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)	17260	1-nitrosopiperazine		C₄H₉N₃O	详情	详情
(II)	17261	1-(4-nitrosopiperazino)-1-ethanone		C₆H₁₁N₃O₂	详情	详情
(III)	17262	1-(4-aminopiperazino)-1-ethanone		C₆H₁₃N₃O	详情	详情
(IV)	17263	4-fluorobenzoyl chloride	403-43-0	C₇H₄ClFO	详情	详情
(V)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VI)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(VII)	17266	benzyl 4-nitrosotetrahydro-1(2H)-pyrazinecarboxylate		C₁₂H₁₅N₃O₃	详情	详情
(VIII)	17267	benzyl 4-aminotetrahydro-1(2H)-pyrazinecarboxylate		C₁₂H₁₇N₃O₂	详情	详情
(IX)	17268	benzyl 4-[(4-fluorobenzoyl)amino]tetrahydro-1(2H)-pyrazinecarboxylate		C₁₉H₂₀FN₃O₃	详情	详情
(X)	17269	4-fluoro-N-piperazinobenzamide		C₁₁H₁₄FN₃O	详情	详情

Extended Information