3,5-Dimethoxy-4-hydroxybenzaldehyde; 4-Hydroxy-3,5-dimethoxybenzaldehyde; Syringaldehyde -Drug Synthesis Database

【结构式】

【分子编号】49243

【品名】3,5-Dimethoxy-4-hydroxybenzaldehyde; 4-Hydroxy-3,5-dimethoxybenzaldehyde; Syringaldehyde

【CA登记号】134-96-3

【分子式】C₉H₁₀O₄

【分子量】182.176

【元素组成】C 59.34% H 5.53% O 35.13%

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：(I)

The protection of the OH group of 4-hydroxy-3,5-dimethoxybenzaldehyde (I) with benzyl bromide and K2CO3 DMF gives the benzyl ether (II), which is condensed with ethyl 2-azidoacetate (III) by means of NaOMe in methanol to yield the 2-azido acrylic acid derivative (IV). The cyclization of (IV) in refluxing xylene affords the indole carboxylate (V), which is deprotected by hydrogenation with H2 over PtO2 in THF/methanol to provide 6-hydroxy-5,7-dimethoxy-1H-indole-2-carboxylic acid methyl ester (I). The condensation of (VI) with 1,2-dibromoethane (VII) by means of K2CO3 in DMF gives the 2-bromoethoxy derivative (VIII), which is treated with sodium azide in DMF to yield the 2-azidoethoxy compound (IX). The hydrolysis of the ester group of (IX) with NaOH in THF/water affords the carboxylic acid (X), which is esterified with 4-nitrophenol (XI) by means of DCC and DMAP in dichloromethane to provide the activated ester (XII). The condensation of (XII) with the tetracyclic compound (XIII) by means of NaH in DMF gives the adduct (XIV), which is finally reduced at the azido group with H2 over Pd/C in THF/HOAc to yield the target compound.

参考文献中间体

合成目标

【1】 Suzawa, T.; et al.; Synthesis of a novel duocarmycin derivative DU-257 and its application to immunoconjugate using poly(ethylene glycol-dipeptidyl linker capable of tumor specific activation. Bioorg Med Chem 2000, 8, 8, 2175.
【2】 Saito, H.; Nagamura, S.; Suzawa, T.; Yamasaki, M.; Ohta, S.; Hanai, N. (Kyowa Hakko Kogyo Co., Ltd.); Toxin conjugates. US 6103236; WO 9635451 .

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)	49243	3,5-Dimethoxy-4-hydroxybenzaldehyde; 4-Hydroxy-3,5-dimethoxybenzaldehyde; Syringaldehyde	134-96-3	C₉H₁₀O₄	详情	详情
(II)	49244	4-Benzyloxy-3,5-dimethoxybenzaldehyde		C₁₆H₁₆O₄	详情	详情
(III)	49245	alpha-azido acetic acid methyl ester		C₃H₅N₃O₂	详情	详情
(IV)	49246	methyl (Z)-2-azido-3-[4-(benzyloxy)-3,5-dimethoxyphenyl]-2-propenoate		C₁₉H₁₉N₃O₅	详情	详情
(V)	49247	methyl 6-(benzyloxy)-5,7-dimethoxy-1H-indole-2-carboxylate		C₁₉H₁₉NO₅	详情	详情
(VI)	49248	methyl 6-hydroxy-5,7-dimethoxy-1H-indole-2-carboxylate		C₁₂H₁₃NO₅	详情	详情
(VII)	10252	1,2-Dibromoethane; Ethylene dibromide	106-93-4	C₂H₄Br₂	详情	详情
(VIII)	49249	methyl 6-(2-bromoethoxy)-5,7-dimethoxy-1H-indole-2-carboxylate		C₁₄H₁₆BrNO₅	详情	详情
(IX)	49250	methyl 6-(2-azidoethoxy)-5,7-dimethoxy-1H-indole-2-carboxylate		C₁₄H₁₆N₄O₅	详情	详情
(X)	49251	6-(2-azidoethoxy)-5,7-dimethoxy-1H-indole-2-carboxylic acid		C₁₃H₁₄N₄O₅	详情	详情
(XI)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(XII)	49252	4-nitrophenyl 6-(2-azidoethoxy)-5,7-dimethoxy-1H-indole-2-carboxylate		C₁₉H₁₇N₅O₇	详情	详情
(XIII)	38365	methyl (3bR,4aS)-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate		C₁₄H₁₄N₂O₃	详情	详情
(XIV)	49253	methyl (3bR,4aS)-6-[[6-(2-azidoethoxy)-5,7-dimethoxy-1H-indol-2-yl]carbonyl]-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate		C₂₇H₂₆N₆O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Alkylation of 4-hydroxy-3,5-dimethoxybenzaldehyde (VII) with 4-isopropylbenzyl chloride (VIII) affords the benzyloxy benzaldehyde (IX). Then, condensation of aldehyde (IX) with hydrazide (VI) furnishes the target N-acyl hydrazone

参考文献中间体

合成目标

【1】 Ling, A.; Plewe, M.; Gonzalez, J.; et al.; Human glucagon receptor antagonists based on alkylidene hydrazides. Bioorg Med Chem Lett 2002, 12, 4, 663.
【2】 Gonzales, J.; Sams, C.; Teng, M. (Alanex Corp.; Novo Nordisk A/S); Glucagon antagonists/inverse agonists. EP 0994848; WO 9901423 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	60848	3-cyano-4-hydroxybenzohydrazide		C₈H₇N₃O₂	详情	详情
(VII)	49243	3,5-Dimethoxy-4-hydroxybenzaldehyde; 4-Hydroxy-3,5-dimethoxybenzaldehyde; Syringaldehyde	134-96-3	C₉H₁₀O₄	详情	详情
(VIII)	33769	1-(chloromethyl)-4-isopropylbenzene	2051-18-5	C₁₀H₁₃Cl	详情	详情
(IX)	60849	4-[(4-isopropylbenzyl)oxy]-3,5-dimethoxybenzaldehyde		C₁₉H₂₂O₄	详情	详情

Extended Information