(E)-(R)-5-(benzo[d]thiazol-2-yl)-5-oxopent-3-yn-2-yl 3-(5-nitrocyclohex-1-en-1-yl)acrylate -Drug Synthesis Database

【结构式】

【分子编号】68749

【品名】(E)-(R)-5-(benzo[d]thiazol-2-yl)-5-oxopent-3-yn-2-yl 3-(5-nitrocyclohex-1-en-1-yl)acrylate

【CA登记号】　

【分子式】C₂₁H₁₈N₂O₅S

【分子量】410.45

【元素组成】C 61.45% H 4.42% N 6.83% O 19.49% S 7.81%

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：(LII)

Partial hydrogenation of propargylic ester (LII) over Lindlar catalyst deactivated with quinoline in toluene gives the triene compound (LIII), which by intramolecular Diels–Alder reaction in NMP at 145 °C followed by epimerization with DBU yields the tricyclic adduct (LIV). Reduction of the nitro group of intermediate (LIV) by means of H2 and Pd/C yields amine (LV), which is finally N-acylated with ethyl chloroformate (VIII) to afford intermediate (L) .
The condensation of acid (XLII) with benzyl hydroxypentynoate (XXIII) by means of pivaloyl chloride, Et3N and DMAP yields ester adduct (LVI), which is submitted to partial hydrogenation in the presence of Lindlar catalyst and quinoline to afford trienoate (LVII). Finally, Diels–Alder cyclization of (LVII) and subsequent epimerization with DBU provides the tricyclic lactone (LI) .

参考文献中间体

合成目标

【1】 Sudhakar, A., Kwok, D.-I., Wu, G.G., Green, M.D., Thiruvengadam, T.K., Lim, N.K., Wang, T., Huang, M. (Schering Corp.). An exo-selective synthesis of himbacine analogs. EP 1846385, JP 2008526974, US 2006217422, US 7772276, WO 2006076452.
【2】 Wu, G., Sudhakar, A.R., Wang, T. et al. (Schering Corp.). Exo- and diastereo- selective synthesis of himbacine analogs. CA 2594871, EP 1848705, EP 2196454, EP 2196468, EP 2206697, JP 2008526972, US 2006247450, WO 2006076415.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(L)	68746	ethyl ((1R,3aR,4aR,6R,8aR,9S,9aS)-9-(benzo[d]thiazole-2-carbonyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl)carbamate		C₂₄H₂₈N₂O₅S	详情	详情
(VIII)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(XXIII)	68723	(R)-benzyl 4-hydroxypent-2-ynoate		C₁₂H₁₂O₃	详情	详情
(XLII)	68738	(R,E)-3-(5-((ethoxycarbonyl)amino)cyclohex-1-en-1-yl)acrylic acid		C₁₂H₁₇NO₄	详情	详情
(LI)	68747	(3S,3aS,4R,4aS,7S,9aS)-benzyl 7-((ethoxycarbonyl)amino)-3-methyl-1-oxo-1,3,3a,4,4a,5,6,7,8,9a-decahydronaphtho[2,3-c]furan-4-carboxylate		C₂₄H₂₉NO₆	详情	详情
(LII)	68749	(E)-(R)-5-(benzo[d]thiazol-2-yl)-5-oxopent-3-yn-2-yl 3-(5-nitrocyclohex-1-en-1-yl)acrylate		C₂₁H₁₈N₂O₅S	详情	详情
(LIII)	68748	(E)-(R,Z)-5-(benzo[d]thiazol-2-yl)-5-oxopent-3-en-2-yl 3-(5-nitrocyclohex-1-en-1-yl)acrylate		C₂₁H₂₀N₂O₅S	详情	详情
(LIV)	68751	(3R,3aS,4R,4aS,7S,9aS)-4-(benzo[d]thiazole-2-carbonyl)-3-methyl-7-nitro-3,3a,4,4a,5,6,7,8-octahydronaphtho[2,3-c]furan-1(9aH)-one		C₂₁H₂₀N₂O₅S	详情	详情
(LV)	68750	(3R,3aS,4R,4aS,7S,8aR,9aS)-7-amino-4-(benzo[d]thiazole-2-carbonyl)-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one		C₂₁H₂₄N₂O₃S	详情	详情
(LVI)	68753	(R)-benzyl 4-(((E)-3-((R)-5-((ethoxycarbonyl)amino)cyclohex-1-en-1-yl)acryloyl)oxy)pent-2-ynoate		C₂₄H₂₇NO₆	详情	详情
(LVII)	68752	(R,Z)-benzyl 4-(((E)-3-((S)-5-((ethoxycarbonyl)amino)cyclohex-1-en-1-yl)acryloyl)oxy)pent-2-enoate		C₂₄H₂₉NO₆	详情	详情

Extended Information