7-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether -Drug Synthesis Database

【结构式】

【分子编号】35823

【品名】7-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether

【CA登记号】

【分子式】C₁₂H₁₄N₂O

【分子量】202.25604

【元素组成】C 71.26% H 6.98% N 13.85% O 7.91%

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：(VII)

Lithiation of 2-chloro-N-methylbenzamide (I) using sec-butyllithium and tetramethyl ethylenediamine, followed by addition of the resulting organolithium derivative to 3-bromo-4,5-dimethoxybenzaldehyde (II) produced hydroxy amide (III), which was cyclized to lactone (IV) upon refluxing with HCl/dioxan. Reduction of the lactone function of (IV) employing DIBAL yielded lactol (V). The intermediate isobenzofuran generated by acidic treatment of lactol (V) experienced a Diels-Alder addition with dimethyl fumarate (VI) to afford adduct (VII). Subsequent aromatization of (VII) to give naphthalene (VIII) was carried out by treatment with boron trifluoride etherate in hot acetonitrile. Selective saponification of the less hindered ester group of (VIII) provided acid (IX). After coupling of (IX) with N-(2-hydroxyethyl)piperazine (X) by means of DCC and HOBt, the title compound was converted to the hydrochloride salt.

参考文献中间体

合成目标

【1】 Takahashi, M.; Yamamoto, Y.; Nakamura, Y.; Kubo, A.; Kotera, J.; Ukita, T.; Ikeo, T.; 1-Arylnaphthalene lignan: A novel scaffold for type 5 phosphodiesterase inhibitor. J Med Chem 1999, 42, 7, 1293.

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)	35828	2-chloro-N-methylbenzamide		C₈H₈ClNO	详情	详情
(II)	35829	3-bromo-4,5-dimethoxybenzaldehyde	6948-30-7	C₉H₉BrO₃	详情	详情
(III)	35830	2-[(3-bromo-4,5-dimethoxyphenyl)(hydroxy)methyl]-6-chloro-N-methylbenzamide		C₁₇H₁₇BrClNO₄	详情	详情
(IV)	35831	3-(3-bromo-4,5-dimethoxyphenyl)-7-chloro-2-benzofuran-1(3H)-one		C₁₆H₁₂BrClO₄	详情	详情
(V)	35832	3-(3-bromo-4,5-dimethoxyphenyl)-7-chloro-1,3-dihydro-2-benzofuran-1-ol		C₁₆H₁₄BrClO₄	详情	详情
(VI)	35018	dimethyl (E)-2-butenedioate	624-49-7	C₆H₈O₄	详情	详情
(VII)	35823	7-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether		C₁₂H₁₄N₂O	详情	详情
(VIII)	35834	dimethyl 1-(3-bromo-4,5-dimethoxyphenyl)-5-chloro-2,3-naphthalenedicarboxylate		C₂₂H₁₈BrClO₆	详情	详情
(IX)	35835	4-(3-bromo-4,5-dimethoxyphenyl)-8-chloro-3-(methoxycarbonyl)-2-naphthoic acid		C₂₁H₁₆BrClO₆	详情	详情
(X)	21893	2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine	103-76-4	C₆H₁₄N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of 4-phenylbutanol (I) with PBr3 gave the corresponding bromide (II). 6-Methoxytryptamine (III) was converted to the hydrochloride salt, and then condensed with formaldehyde under Pictet-Spengler conditions to furnish the pyridoindole system (IV). Alkylation of amine (IV) with bromide (II) then gave the phenylbutyl amine (V). Finally, O-demethylation of (V) employing BBr3 yielded the title compound.

参考文献中间体

合成目标

【1】 Becker, R.E.; Thornton, S.L.; Moriearty, P.L.; Transdermal patch delivery of acetylcholinesterase inhibitors. Methods Find Exp Clin Pharmacol 1993, 15, 6, 407.

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)	27291	4-phenyl-1-butanol	3360-41-6	C₁₀H₁₄O	详情	详情
(II)	27300	1-(4-bromobutyl)benzene; (4-bromobutyl)benzene	13633-25-5	C₁₀H₁₃Br	详情	详情
(III)	35822	6-Methoxytryptamine; 3-(2-Aminoethyl)-6-methoxyindole; 2-(6-Methoxy-1H-indol-3-yl)-1-ethanamine; 2-(6-Methoxy-1H-indol-3-yl)ethylamine	3610-36-4	C₁₁H₁₄N₂O	详情	详情
(IV)	35823	7-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether		C₁₂H₁₄N₂O	详情	详情
(V)	35824	7-methoxy-2-(4-phenylbutyl)-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2-(4-phenylbutyl)-2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether		C₂₂H₂₆N₂O	详情	详情

Extended Information