methyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】16422

【品名】methyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate

【CA登记号】

【分子式】C₈H₁₁NO₂

【分子量】153.18088

【元素组成】C 62.73% H 7.24% N 9.14% O 20.89%

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-(LVI)

14) It is noteworthy that Regan et al. described a very concise synthesis of racemic epibatidine. The key step was a reductive Pd-catalyzed Heck-type coupling of the known starting materials olefin (LVI) and 2-chloro-5-iodopyridine (LVII). The desired exo-isomer (LVIII) was formed stereoselectively.

参考文献中间体

合成目标

【1】 Clayton, S.C.; Regan, A.C.; A total synthesis of (±)-epibatidine. Tetrahedron Lett 1993, 34, 7493-6.
【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	分子式	供应商	用于合成
rac-(LIV)	16420	methyl (1S,4R)-2-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hepta-2,5-diene-7-carboxylate	C₁₅H₁₅NO₄S	详情	详情
rac-(LV)	16421	methyl (1S,4R)-2-[(4-methylphenyl)sulfonyl]-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate	C₁₅H₁₇NO₄S	详情	详情
rac-(LVI)	16422	methyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate	C₈H₁₁NO₂	详情	详情
rac-(LVII)	16424	methyl (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate	C₁₃H₁₅ClN₂O₂	详情	详情
(LVII)	16423	2-chloro-5-iodopyridine	C₅H₃ClIN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Intermediate (III) was prepared by condensation of epoxide (I) with piperazine (II). After removal of the carbobenzoxy protecting group of (III) by catalytic hydrogenation, the resulting amine (IV) was coupled to the valine derivative (V) using EDC to afford amide (VI). Subsequent cleavage of the Boc protecting group of (VI) under acidic conditions gave (VII), which was finally alkylated with the benzodioxolylmethyl halide (VIII) to provide the target compound.

参考文献中间体

合成目标

【1】 Chen, X.; Kempf, D.J.; Sham, H.L.; Green, B.E.; Molla, A.; Korneyeva, M.; Vasavanonda, S.; Wideburg, N.E.; Saldivar, A.; Marsh, K.C.; McDonald, E.; Norbeck, D.W.; Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands. Bioorg Med Chem Lett 1998, 8, 24, 3531.
【2】 Chen, X.; Mohammadi, F.; Norbeck, D.W.; Kempf, D.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds.. WO 9959994 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	14522	benzyl N-[(1S)-1-[(2S)oxiranyl]-2-phenylethyl]carbamate	C₁₈H₁₉NO₃	详情	详情
(II)	16422	methyl (1R,4S)-7-azabicyclo[2.2.1]hept-2-ene-7-carboxylate	C₈H₁₁NO₂	详情	详情
(III)	30251	tert-butyl (3S)-4-((2R,3S)-3-[[(benzyloxy)carbonyl]amino]-2-hydroxy-4-phenylbutyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate	C₃₂H₄₆N₄O₆	详情	详情
(IV)	30252	tert-butyl (3S)-4-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate	C₂₄H₄₀N₄O₄	详情	详情
(V)	30255	(2S)-2-([[(2-isopropyl-1,3-thiazol-4-yl)methoxy]carbonyl]amino)-3-methylbutyric acid	C₁₃H₂₀N₂O₄S	详情	详情
(VI)	30253	tert-butyl (3S)-3-[(tert-butylamino)carbonyl]-4-((2R,3S)-2-hydroxy-3-[[(2S)-2-([[(2-isopropyl-1,3-thiazol-4-yl)methoxy]carbonyl]amino)-3-methylbutanoyl]amino]-4-phenylbutyl)-1-piperazinecarboxylate	C₃₇H₅₈N₆O₇S	详情	详情
(VII)	30254	(2-isopropyl-1,3-thiazol-4-yl)methyl (1S)-1-[[((1S,2R)-1-benzyl-3-[(2S)-2-[(tert-butylamino)carbonyl]piperazinyl]-2-hydroxypropyl)amino]carbonyl]-2-methylpropylcarbamate	C₃₂H₅₀N₆O₅S	详情	详情
(VIII)	28617	5-(chloromethyl)-1,3-benzodioxole	C₈H₇ClO₂	详情	详情

Extended Information