(1R,2R,3R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane -Drug Synthesis Database

【结构式】

【分子编号】47191

【品名】(1R,2R,3R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane

【CA登记号】

【分子式】C₁₈H₂₃N₃O

【分子量】297.40024

【元素组成】C 72.7% H 7.8% N 14.13% O 5.38%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

Treatment of azabicyclo[3.2.1]octene derivative (I) with lithiated compound (II) in THF followed by quenching with trifluoroacetic acid yields tropane (III), whose oxadiazole group is converted into a methyl ester by treatment with nickel boride (Ni2B) and HCl in refluxing methanol to provide the 2-beta,3-alpha stereoisomer (IV). Finally, the desired nortropane compound is obtained by refluxing tropane (IV) with alpha-chloroethyl chloroformate (ACE-Cl) in dichloromethane followed by solvolysis with methanol.

参考文献中间体

合成目标

【1】 Kuhar, M.J.; Blough, B.E.; Holmquist, C.R.; Carroll, F.I.; Abraham, P.; 3alpha-(4-Substituted phenyl) mortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter. Bioorg Med Chem Lett 2000, 10, 21, 2445.
【2】 Holmquist, C.R.; et al.; 3alpha-(4'-Substituted phenyl)tropane-2beta-carboxylic acid methyl esters: Novel ligands with high affinity and selectivity at the dopamine transporter. J Med Chem 1996, 39, 21, 4139.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	47190	(1R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-8-azabicyclo[3.2.1]oct-2-ene	C₁₁H₁₅N₃O	详情	详情
(II)	29629	(4-methylphenyl)lithium	C₇H₇Li	详情	详情
(III)	47191	(1R,2R,3R,5S)-8-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane	C₁₈H₂₃N₃O	详情	详情
(IV)	47192	methyl (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate	C₁₇H₂₃NO₂	详情	详情

Extended Information