(3S,4R)-3-(6-chloro-3-pyridinyl)-4-nitrocyclohexanone -Drug Synthesis Database

【结构式】

【分子编号】16383

【品名】(3S,4R)-3-(6-chloro-3-pyridinyl)-4-nitrocyclohexanone

【CA登记号】

【分子式】C₁₁H₁₁ClN₂O₃

【分子量】254.67272

【元素组成】C 51.88% H 4.35% Cl 13.92% N 11% O 18.85%

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：rac-(XVI)

4) Szantay et al. reported a practical route to epibatidine by using commonly available starting materials under convenient reaction conditions. The alpha,beta-unsaturated ketone (XV) was synthesized by Wittig reaction of 6-chloronicotinaldehyde and the appropriate phosphorane. Ring closure took place by treatment of compound (XV) with KF/Al2O3. Reduction of the keto group followed by mesylation and subsequent reduction of the nitro group afforded amine (XVII). Upon boiling in toluene, (XVII) was immediately transformed into the undesired endo-isomer of epibatidine (XVIII). Taking advantage of Fletcher's endo- to exo-epimerization, (XVIII) was converted into racemic epibatidine in moderate yield. The advantage of this route is that no protection and consequently no deprotection steps are involved. But the combined yield in the last two steps is only 30%.

参考文献中间体

合成目标

【1】 Fletcher, S.R.; Baker, R.; Chambers, M.S.; Hobbs, S.C.; Mitchell, P.J.; The synthesis of (+)- and (-)-epibatidine. J Chem Soc Ser Chem Commun 1993, 1216-8.
【2】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210.
【3】 Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Szántay, C. Jr.; Major-Temesváry, E.; Blaskó, G.; A practical route to epibatidine. Tetrahedron Lett 1994, 35, 19, 3171-4.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
rac-(XVI)	16383	(3S,4R)-3-(6-chloro-3-pyridinyl)-4-nitrocyclohexanone		C₁₁H₁₁ClN₂O₃	详情	详情
rac-(XVII)	16384	(1R,2S,4R)-2-(6-chloro-3-pyridinyl)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]cyclohexanamine; (1R,2S,4R)-2-(6-chloro-3-pyridinyl)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]cyclohexylamine		C₁₄H₂₁ClN₂OS	详情	详情
(rac-I)	16385	(+)-Epibatidine hydrochloride; (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	140111-52-0	C₁₁H₁₃ClN₂	详情	详情
rac-(XVIII)	16385	(+)-Epibatidine hydrochloride; (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	140111-52-0	C₁₁H₁₃ClN₂	详情	详情
(XV)	16382	(E)-1-(6-chloro-3-pyridinyl)-6-nitro-1-hexen-3-one		C₁₁H₁₁ClN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(rac-XVI)

5) Later on, Szantay's group modified the above described procedure based on a polarity reversal approach (8). Compound (XVI) was thus converted to the ring closure precursor (XIX) in 7 steps. Base-catalyzed ring closure of (XIX) afforded racemic epibatidine.

参考文献中间体

合成目标

【1】 Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Szántay, C. Jr.; Major-Temesvary, E.; Blasko,G.; A practical enantioselective synthesis of epibatidine. Tetrahedron 1996, 52, 11053-62.
【2】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(rac-XVI)	16383	(3S,4R)-3-(6-chloro-3-pyridinyl)-4-nitrocyclohexanone		C₁₁H₁₁ClN₂O₃	详情	详情
(rac-I)	16385	(+)-Epibatidine hydrochloride; (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	140111-52-0	C₁₁H₁₃ClN₂	详情	详情
rac-(XIX)	16386	N-[(1S,2R,4S)-4-amino-2-(6-chloro-3-pyridinyl)cyclohexyl]-4-methyl-N-[(4-methylphenyl)sulfonyl]benzenesulfonamide		C₂₅H₂₈ClN₃O₄S₂	详情	详情

Extended Information