5-isoquinolinol -Drug Synthesis Database

【结构式】

【分子编号】18668

【品名】5-isoquinolinol

【CA登记号】2439-04-5

【分子式】C₉H₇NO

【分子量】145.16072

【元素组成】C 74.47% H 4.86% N 9.65% O 11.02%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

Alkylation of 5-hydroxyisoquinoline (I) with bromide (II) in DMF at 80 C afforded isoquinolinium salt (III). This was reduced to tetrahydroisoquinoline (IV) by catalytic hydrogenation in the presence of Pd/C. Finally, Mannich reaction with formaldehyde and perhydroazepine (V) in THF-water at r.t. provided the target compound.

参考文献中间体

合成目标

【1】 Yuen, P.; Schelkun, R.M.; Szoke, B.; Tarczy-Hornoch K.; Synthesis and structure-activity relationship of substituted 1,2,3,4-tetrahydroisoquinolines as N-type calcium channel blockers. Bioorg Med Chem Lett 1998, 8, 18, 2415.

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)	18668	5-isoquinolinol	2439-04-5	C₉H₇NO	详情	详情
(II)	18669	1-(4-bromo-1-phenylbutyl)benzene		C₁₆H₁₇Br	详情	详情
(III)	18670	2-(4,4-diphenylbutyl)-5-hydroxyisoquinolinium bromide		C₂₅H₂₄BrNO	详情	详情
(IV)	18671	2-(4,4-diphenylbutyl)-1,2,3,4-tetrahydro-5-isoquinolinol		C₂₅H₂₇NO	详情	详情
(V)	18672	azepane	111-49-9	C₆H₁₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Nitration of 2,6-dichlorobenzaldehyde (I) with 70% HNO3 in concentrated H2SO4 at ice-bath temperature provided the 3-nitro derivative (II). This was reduced with NaBH4 in MeOH at 10 C to the alcohol (III), which was treated with mesyl chloride and triethylamine in dichloromethane to give mesylate (IV). Alkylation of 5-hydroxyisoquinoline (V) with mesylate (IV) in the presence of NaH in DMF yielded ether (VI). Subsequent reduction of the nitro group of (VI) with hydrazine and FeCl3 provided amine (VII), which was finally acylated with Ac2O in dichloroethane at 70 C to furnish the target acetamide.

参考文献中间体

合成目标

【1】 Satoh, S.; Kayakiri, H.; Abe, Y.; et al.; A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 1. Construction of the basic framework. J Med Chem 1998, 41, 4, 564.
【2】 Yoshida, Y.; Barrett, D.; Azami, H.; Morinaga, C.; Matsumoto, Y.; Takasugi, H.; Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity. Bioorg Med Chem Lett 1998, 8, 14, 1897.

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)	27507	2,6-dichlorobenzaldehyde	83-38-5	C₇H₄Cl₂O	详情	详情
(II)	27508	2,6-dichloro-3-nitrobenzaldehyde		C₇H₃Cl₂NO₃	详情	详情
(III)	18590	(2,6-dichloro-3-nitrophenyl)methanol		C₇H₅Cl₂NO₃	详情	详情
(IV)	19295	2,6-dichloro-3-nitrobenzyl methanesulfonate		C₈H₇Cl₂NO₅S	详情	详情
(V)	18668	5-isoquinolinol	2439-04-5	C₉H₇NO	详情	详情
(VI)	27509	2,6-dichloro-3-nitrobenzyl 5-isoquinolinyl ether		C₁₆H₁₀Cl₂N₂O₃	详情	详情
(VII)	27510	2,4-dichloro-3-[(5-isoquinolinyloxy)methyl]aniline		C₁₆H₁₂Cl₂N₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

Alkylation of 5-hydroxyisoquinoline (VII) with epibromohydrin (VIII) produced the glycidyl ether (IX). Subsequent epoxide ring opening in (IX) with aniline (VI) furnished the target (isoquinolyloxy)propanolamine.

参考文献中间体

合成目标

【1】 Aubriot, S.; et al.; New series of aryloxypropanolamines with both human beta3-adrenoceptor agonistic activity and free radical scavenging properties. Bioorg Med Chem Lett 2002, 12, 2, 209.

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)	59679	4-[3-(4-aminophenoxy)propyl]-2,6-di(tert-butyl)phenol		C₂₃H₃₃NO₂	详情	详情
(VII)	18668	5-isoquinolinol	2439-04-5	C₉H₇NO	详情	详情
(VIII)	29679	2-(bromomethyl)oxirane	3132-64-7	C₃H₅BrO	详情	详情
(IX)	59680	5-isoquinolinyl 2-oxiranylmethyl ether; 5-(2-oxiranylmethoxy)isoquinoline		C₁₂H₁₁NO₂	详情	详情

Extended Information