4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-1-azoniabicyclo[3,1,0]hexane tetrafluoroborate -Drug Synthesis Database

【结构式】

【分子编号】30366

【品名】4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-1-azoniabicyclo[3,1,0]hexane tetrafluoroborate

【CA登记号】

【分子式】C₁₇H₂₆BF₄NO

【分子量】347.2041928

【元素组成】C 58.81% H 7.55% B 3.11% F 21.89% N 4.03% O 4.61%

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：(IV)

The methylation of 2-methyl-3-propyl-3-(3-methoxyphenyl)-1-pyrroline (I) with dimethyl sulfate in refluxing butanone gives 1-methyl-3-propyl-2-exo-methylene-3-(3-methoxyphenyl)pyrrolidine (II), which by reaction with HBF4 in ethanol is converted into 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)pyrrolinium tetrafluoroborate (III). The methylation of (III) with diazomethane in dichloromethane ether yields 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)-1,2-ethylenepyrrolidinium tetrafluoroborate (IV), which by heating at 180 C and neutralization with NaOH affords 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)-1,4,5,6-tetrahydropyridine (V). The reduction of (V) with NaBH4 in THF gives 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)piperidine (VI), which is finally treated with 48% HBr in refluxing acetic acid.

参考文献中间体

合成目标

【1】 Zimmerman, D.M. (Eli Lilly and Company); 1,3,4-Trisubstituted-4-arylpiperidines and their preparation. BE 0833044; DE 2539452; FR 2283679; FR 2299337; GB 1525584; JP 7648670; JP 7783572 .
【2】 Castaner, J.; Serradell, M.N.; Picedanol Hydrochloride. Drugs Fut 1984, 9, 3, 204.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	30363	4-(3-methoxyphenyl)-5-methyl-4-propyl-3,4-dihydro-2H-pyrrole; methyl 3-(5-methyl-4-propyl-3,4-dihydro-2H-pyrrol-4-yl)phenyl ether	C₁₅H₂₁NO	详情	详情
(II)	30364	methyl 3-(1-methyl-2-methylene-3-propyl-3-pyrrolidinyl)phenyl ether; 3-(3-methoxyphenyl)-1-methyl-2-methylene-3-propylpyrrolidine	C₁₆H₂₃NO	详情	详情
(III)	30365	4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-3,4-dihydro-2H-pyrrolium tetraflluoroborate	C₁₆H₂₄BF₄NO	详情	详情
(IV)	30366	4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-1-azoniabicyclo[3,1,0]hexane tetrafluoroborate	C₁₇H₂₆BF₄NO	详情	详情
(V)	30367	4-(3-methoxyphenyl)-1,5-dimethyl-4-propyl-1,2,3,4-tetrahydropyridine; 3-(1,5-dimethyl-4-propyl-1,2,3,4-tetrahydro-4-pyridinyl)phenyl methyl ether	C₁₇H₂₅NO	详情	详情
(VI)	30368	(3S,4R)-4-(3-methoxyphenyl)-1,3-dimethyl-4-propylpiperidine; 3-[(3S,4R)-1,3-dimethyl-4-propylpiperidinyl]phenyl methyl ether	C₁₇H₂₇NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

A related method for the synthesis of the title compound has been reported. After esterification of 5-iodosalicylic acid (I), the methyl ester (II) is reacted with 1,2-dibromoethane to give bromide (III). Coupling of aryl iodide (III) with 3-butyn-1-ol (IV) leads to adduct (V). Displacement of bromide (V) with (R)-p-chlorobenzhydryl piperazine (VI) furnishes piperazine (VII). Then, ester group ammonolysis in (VII) leads to amide (VIII). Coupling of alcohol (VIII) with phenoxycarbonylamino phenoxyformate (IX) under Mitsunobu conditions furnishes the protected N-hydroxy carbamate (X). Finally, treatment of (X) with methanolic ammonia provides the desired N-hydroxyurea derivative

参考文献中间体

合成目标

【1】 Cai, X.; Arrington, M.; Bayless, L.; et al.; Discovery of UCB 35440: A potent and orally active dual acting 5-lipoxygenase inhibitor and H1 receptor antagonist. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 317.

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)	60359	2-hydroxy-5-iodobenzoic acid		C₇H₅IO₃	详情	详情
(II)	37875	methyl 2-hydroxy-5-iodobenzoate		C₈H₇IO₃	详情	详情
(III)	30366	4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-1-azoniabicyclo[3,1,0]hexane tetrafluoroborate		C₁₇H₂₆BF₄NO	详情	详情
(IV)	32507	3-butyn-1-ol	927-74-2	C₄H₆O	详情	详情
(V)	60361	methyl 2-[(2-bromoethyl)oxy]-5-(4-hydroxy-1-butynyl)benzoate		C₁₄H₁₅BrO₄	详情	详情
(VI)	30404	1-[(R)-(4-chlorophenyl)(phenyl)methyl]piperazine		C₁₇H₁₉ClN₂	详情	详情
(VII)	60362	methyl 2-[(2-{4-[(4-chlorophenyl)(phenyl)methyl]-1-piperazinyl}ethyl)oxy]-5-(4-hydroxy-1-butynyl)benzoate		C₃₁H₃₃ClN₂O₄	详情	详情
(VIII)	60367	2-[(2-{4-[(4-chlorophenyl)(phenyl)methyl]-1-piperazinyl}ethyl)oxy]-5-(4-hydroxy-1-butynyl)benzamide		C₃₀H₃₂ClN₃O₃	详情	详情
(IX)	19646	1-[([[(phenoxycarbonyl)oxy]amino]carbonyl)oxy]benzene		C₁₄H₁₁NO₅	详情	详情
(X)	60363	methyl 2-[(2-{4-[(4-chlorophenyl)(phenyl)methyl]-1-piperazinyl}ethyl)oxy]-5-[4-([(phenyloxy)carbonyl]{[(phenyloxy)carbonyl]oxy}amino)-1-butynyl]benzoate		C₄₅H₄₂ClN₃O₈	详情	详情

Extended Information