5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine -Drug Synthesis Database

【结构式】

【分子编号】62988

【品名】5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine

【CA登记号】

【分子式】C₁₁H₈BrN₅

【分子量】290.12222

【元素组成】C 45.54% H 2.78% Br 27.54% N 24.14%

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：AGN-192076

4) The reaction of amine (I) with phenyl cyanate (V) and KH in THF gives N-(5-bromoquinoxalin-6-yl)cyanamide (VI), which is cyclized with ethyl glycinate (VII) in refluxing ethanol to yield 2-(5-bromoquinoxalin-6-imino)imidazolidin-4-one (AGN-192119). 5) The reaction of cyanamide (VI) with 2-aminoacetaldehyde diethyl acetal (VIII) affords N1-(5-bromoquinoxalin-6-yl)-N3-(2,2-diethoxyethyl)guanidine (IX), which is cyclized by means of HCl to the hydroxyimidazoline (X). Finally, this compound is treated with NaOH to afford 5-bromo-6-(2-imidazolylamino)quinoxaline (AGN-192076).

参考文献中间体

合成目标

【1】 Tang-Liu, D.; Burke, J.; Garst, M.; Harcourt, D.; Acheampong, A.; Breau, A.; Munk, S.A.; Wong, H.; Lai, R.; Wheeler, L.; Synthesis and characterization of degradation products and metabolites of brimonidine - A potent alpha2 adrenergic agonist. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 021.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
AGN-192119	62987	2-[(5-bromo-6-quinoxalinyl)imino]-4-imidazolidinone		C₁₁H₈BrN₅O	详情	详情
AGN-192076	62988	5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine		C₁₁H₈BrN₅	详情	详情
(I)	10328	5-Bromo-6-quinoxalinamine; 5-Bromo-6-quinoxalinylamine		C₈H₆BrN₃	详情	详情
(V)	62986	phenyl cyanate		C₇H₅NO	详情	详情
(VI)	10330	N-(5-Bromo-6-quinoxalinyl)cyanamide		C₉H₅BrN₄	详情	详情
(VII)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(VIII)	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
(IX)	10332	N-(5-Bromo-6-quinoxalinyl)-N'-(2,2-diethoxyethyl)guanidine		C₁₅H₂₀BrN₅O₂	详情	详情
(X)	10333	2-[(5-Bromo-6-quinoxalinyl)amino]-4,5-dihydro-1H-imidazol-5-ol		C₁₁H₁₀BrN₅O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Intramolecular cyclization of p-hydroxy-4-chlorobutyrophenone (I) under alkaline conditions yields cyclopropyl(4-hydroxyphenyl) ketone (II). The phenolic hydroxyl group is then alkylated by 1-bromo-3-chloropropane (III) to furnish the chloropropyl ether (IV). Subsequent condensation of alkyl chloride (IV) with piperazine (V) gives rise to the N-substituted piperazine (VI). This is then coupled with N-Boc-L-alanine (VII) in the presence of EDC/DMAP to afford amide (VIII) (1, 2). After acidic cleavage of the N-Boc protecting group, the resultant monosubstituted piperazine (IX) is acylated by furanoyl chloride (X) to furnish the target furamide derivative

参考文献中间体

合成目标

【1】 Black, L.A.; Faghih, R.; Liu, H.; et al.; Acyl-D-alanine amides: Selective histamine H3 receptor antagonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 323.
【2】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. WO 0166534 .
【3】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. US 2001049367; US 6559140 .

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)	62995			C₁₀H₁₁ClO₂	详情	详情
(II)	27425	cyclopropyl(4-hydroxyphenyl)methanone		C₁₀H₁₀O₂	详情	详情
(III)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(IV)	62988	5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine		C₁₁H₈BrN₅	详情	详情
(V)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VI)	62996			C₁₇H₂₄N₂O₂	详情	详情
(VII)	15859	Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid	7764-95-6	C₈H₁₅NO₄	详情	详情
(VIII)	63042			C₂₈H₂₃ClN₂O₂	详情	详情
(IX)	63043			C₁₇H₁₅ClN₂O₂	详情	详情
(X)	26093	2-Furoyl chloride	527-69-5	C₅H₃ClO₂	详情	详情

Extended Information