2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】37025

【品名】2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione

【CA登记号】574-98-1

【分子式】C₁₀H₈BrNO₂

【分子量】254.08306

【元素组成】C 47.27% H 3.17% Br 31.45% N 5.51% O 12.59%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：

Synthesis of intermediate (X): 4-Hydroxypiperidine (V) is protected with ethyl chloroformate to give (VI), which is then condensed with bromodiphenylmethane in the presence of sodium carbonate yielding (VII). AIkali hydrolysis of (VII) gives (VIII), which is then treated with N-(2-bromoethyl)phthalimide to yield (IX). (IX) is then deprotected by a treatment of 80% hydrazine hydrate, producing (X).

参考文献中间体

合成目标

【1】 Tasaka, K.; TMK-688. Drugs Fut 1988, 13, 12, 1056.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(IIb)	12079	Bromodiphenylmethane; 1-[Bromo(phenyl)methyl]benzene; Benzhydrylbromide	776-74-9	C₁₃H₁₁Br	详情	详情
(V)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(VI)	22709	ethyl 4-hydroxy-1-piperidinecarboxylate		C₈H₁₅NO₃	详情	详情
(VII)	12080	ethyl 4-(benzhydryloxy)tetrahydro-1(2H)-pyridinecarboxylate		C₂₁H₂₅NO₃	详情	详情
(VIII)	12081	4-(Benzhydryloxy)piperidine; Benzhydryl 4-piperidinyl ether		C₁₈H₂₁NO	详情	详情
(IX)	22713	2-[2-[4-(benzhydryloxy)-1-piperidinyl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₈H₂₈N₂O₃	详情	详情
(X)	22707	2-[4-(benzhydryloxy)-1-piperidinyl]ethylamine; 2-[4-(benzhydryloxy)-1-piperidinyl]-1-ethanamine		C₂₀H₂₆N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 2-nitroimidazole (I) with N-(2-bromoethyl)phthalimide (II) by means of NaH in DMSO gives N-[2-(2-nitroimidazol-1-yl)ethyl]phthalimide (III), which is treated with hydrazine in ethanol/water to yield 2-(2-nitroimidazol-1-yl)ethylamine (IV). Finally this amine is condensed with 9-chloroacridine by means of TEA.

参考文献中间体

合成目标

【1】 Bloomer, W.D.; Papadopoulou, M.V.; Nitroheterocyclic-linked acridines as DNA-targeting bioreductive agents. Drugs Fut 1993, 18, 3, 231.
【2】 DeCarneri, I.; Giraldi, P.N.; Mariotti, V.; Studies on antiprotozoans. Synthesis and biological activity of some styrylimidazole derivatives. J Med Chem 1968, 11, 60-70.
【3】 Adams, G.E.; Ahmed, I.; Stratford, I.J. (Gerald Edward Adams; Ian James Stratford; Israr Ahmed); Bis(nitro-1-imidazolyl alkylamine) platinum complexes useful in radiotheraphy or chemotherapy. GB 2131020 .

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)	10145	2-Nitro-1H-imidazole; 2-Nitroimidazole	527-73-1	C₃H₃N₃O₂	详情	详情
(II)	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(III)	41283	2-[2-(2-nitro-1H-imidazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione		C₁₃H₁₀N₄O₄	详情	详情
(IV)	41284	2-(2-nitro-1H-imidazol-1-yl)ethylamine; 2-(2-nitro-1H-imidazol-1-yl)-1-ethanamine		C₅H₈N₄O₂	详情	详情
(V)	32672	9-chloroacridine	1207-69-8	C₁₃H₈ClN	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The intermediate amine (IV) was prepared by alkylation of N-(2-isopropoxyphenyl)piperazine (I) with N-(2-bromoethyl)phthalimide (II), followed by removal of the phthaloyl group upon treatment with methylhydrazine.

参考文献中间体

合成目标

【1】 Murray, W.V.; Jolliffe, L.; Pulito, V.; Li, X.; Novel arylpiperazines as selective alpha1-adrenergic receptor antagonists. Bioorg Med Chem Lett 2000, 10, 10, 1093.
【2】 Mulcahy, L.; Pulito, V.; Villani, F.; Li, X.; Murray, W.; Maryanoff, C.; Jolliffe, L.; Reitz, A. (Ortho-McNeil Pharmaceutical, Inc.); Arylsubstd. piperazines useful in the treatment of benign prostatic hyperplasia. EP 0984777; US 6071915; WO 9851298 .

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)	35066	isopropyl 2-(1-piperazinyl)phenyl ether; 1-(2-isopropoxyphenyl)piperazine		C₁₃H₂₀N₂O	详情	详情
(II)	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(III)	43364	2-[2-[4-(2-isopropoxyphenyl)-1-piperazinyl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₃H₂₇N₃O₃	详情	详情
(IV)	43365	2-[4-(2-isopropoxyphenyl)-1-piperazinyl]ethylamine; 2-[4-(2-isopropoxyphenyl)-1-piperazinyl]-1-ethanamine		C₁₅H₂₅N₃O	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The condensation of ethyl allophanate (I) with diphenylhydrazine (II) produced 1,2-diphenylurazole (III). Alkylation of (III) with N-(2-bromoethyl)phthalimide (IV) in the presence of potassium tert-butoxide afforded the 4-(2-phthalimidoethyl)urazole (V), and the subsequent hydrazinolysis of the phthalimide group of (V) yielded the amino derivative (VI). Then, coupling of (VI) with N-(benzyloxycarbonyl)arginine (VII) via activation with 1,1'-carbonyldiimidazole (CDI) furnished amide (VIII). Deprotection of the N-benzyloxycarbonyl group of (VIII) to give (IX) was effected by catalytic hydrogenation over Pd/C.

参考文献中间体

合成目标

【1】 Gaida, W.; Schnorrenberg, G.; Dollinger, H.; Doods, H.N.; Esser, F.; Rudolf, K.; Mihm, G. (Boehringer Ingelheim Pharma KG); Novel substd. amino acid derivs., process for their preparation and pharmaceutical compsns. containing them. DE 19816929 .

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)	37022	ethyl aminocarbonylcarbamate	626-36-8	C₄H₈N₂O₃	详情	详情
(II)	37023	1,2-diphenylhydrazine	122-66-7	C₁₂H₁₂N₂	详情	详情
(III)	37024	1,2-diphenyl-1,2,4-triazolidine-3,5-dione		C₁₄H₁₁N₃O₂	详情	详情
(IV)	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(V)	37026	2-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-1H-isoindole-1,3(2H)-dione		C₂₄H₁₈N₄O₄	详情	详情
(VI)	37027	4-(2-aminoethyl)-1,2-diphenyl-1,2,4-triazolidine-3,5-dione		C₁₆H₁₆N₄O₂	详情	详情
(VII)	37028	(2S)-5-[[amino(imino)methyl]amino]-2-[[(benzyloxy)carbonyl]amino]pentanoic acid		C₁₄H₂₀N₄O₄	详情	详情
(VIII)	37029	benzyl (1S)-4-[[amino(imino)methyl]amino]-1-([[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl)butylcarbamate		C₃₀H₃₄N₈O₅	详情	详情
(IX)	37030	(2S)-2-amino-5-[[amino(imino)methyl]amino]-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]pentanamide		C₂₂H₂₈N₈O₃	详情	详情

合成路线5

该中间体在本合成路线中的序号：(IV)

Oxazinone (II) was prepared by cyclization of the unsaturated keto acid (I) with hydroxylamine. Subsequent radical bromination of (II) with N-bromosuccinimide (NBS) provided the alpha-bromobenzyl derivative (III). Alkylation of 3-chlorophenyl piperazine (IV) with N-(2-bromoethyl)phthalimide (V) gave adduct (VI). Further hydrazinolysis of the phthaloyl group of (VI) yielded the primary amine (VII). Finally, condensation between bromide (III) and amine (VII) in refluxing THF furnished the title 5-amino oxazinone derivative.

参考文献中间体

合成目标

【1】 Rubat, C.; Bebot, M.; Fialip, J.; Coudert, P.; Courteix, C.; Couquelet, J.; Synthesis and analgesic effects of 5-[4-(arylpiperazin-1-yl)alkylamino]-4-benzyl-3-methyl-1,2-oxazin-6-ones. Arzneim-Forsch Drug Res 2000, 50, 4, 353.

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)	46968	(E)-3-benzyl-4-oxo-2-pentenoic acid		C₁₂H₁₂O₃	详情	详情
(II)	46969	4-benzyl-3-methyl-6H-1,2-oxazin-6-one		C₁₂H₁₁NO₂	详情	详情
(III)	46970	4-[bromo(phenyl)methyl]-3-methyl-6H-1,2-oxazin-6-one		C₁₂H₁₀BrNO₂	详情	详情
(IV)	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(V)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(VI)	46971	2-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₀H₂₀ClN₃O₂	详情	详情
(VII)	46972	2-[4-(3-chlorophenyl)-1-piperazinyl]-1-ethanamine; 2-[4-(3-chlorophenyl)-1-piperazinyl]ethylamine		C₁₂H₁₈ClN₃	详情	详情

Extended Information