5-methoxy-3,4-dihydro-1(2H)-naphthalenone -Drug Synthesis Database

【结构式】

【分子编号】18568

【品名】5-methoxy-3,4-dihydro-1(2H)-naphthalenone

【CA登记号】33892-75-0

【分子式】C₁₁H₁₂O₂

【分子量】176.21508

【元素组成】C 74.98% H 6.86% O 18.16%

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)

Alkylation of 5-methoxytetralone (I) with n-butyl iodide in the presence of lithium diisopropylamide (LDA) in dimethoxyethane afforded a mixture of mono- (II) and dialkylated (III) compounds that were separated by column chromatography. Hydrolysis of methoxy group of (III) by treatment with AlBr3 in refluxing benzene yielded phenol (IV), which was converted to ether (VI) by treatment with 2-(chloromethyl)quinoline (V) and K2CO3. The reduction of ketone (VI) with NaBH4 in MeOH provided racemic alcohol (VII). Resolution of racemate (VII) was performed by esterification with (S)-O-methylmandeloyl chloride (VIII), followed by chromatographic separation of the diastereomeric mixture. Then, basic hydrolysis of pure diastereomer (IX) provided the (+)-enantiomer. Alternatively, asymmetric reduction of tetralone (VI) with LiAlH4 in cold THF in the presence of the chiral auxiliary (S)-4-anilino-3-methylamino-1-butanol (X) or (S)-2-amino-3-methyl-1,1-diphenyl-1-butanol (XI) afforded (+)-alcohol (respectively).

参考文献中间体

合成目标

【1】 Yatabe, T.; Kayakiri, H.; Kawai, Y.; Oku, T.; Tanaka, H.; Studies on 5-lipoxygenase inhibitors. II. Discovery, optical resolution and enantioselective synthesis of FR110302, a highly potent non-redox type 5-lipoxygenase inhibitor. Chem Pharm Bull 1998, 46, 10, 1556.

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)	18568	5-methoxy-3,4-dihydro-1(2H)-naphthalenone	33892-75-0	C₁₁H₁₂O₂	详情	详情
(II)	18569	2-butyl-5-methoxy-3,4-dihydro-1(2H)-naphthalenone		C₁₅H₂₀O₂	详情	详情
(III)	18570	2,2-dibutyl-5-methoxy-3,4-dihydro-1(2H)-naphthalenone		C₁₉H₂₈O₂	详情	详情
(IV)	18571	2,2-dibutyl-5-hydroxy-3,4-dihydro-1(2H)-naphthalenone		C₁₈H₂₆O₂	详情	详情
(V)	13162	2-(Chloromethyl)quinoline; alpha-Chloroquinaldine	4377-41-7	C₁₀H₈ClN	详情	详情
(VI)	18573	2,2-dibutyl-5-(2-quinolinylmethoxy)-3,4-dihydro-1(2H)-naphthalenone		C₂₈H₃₃NO₂	详情	详情
(VII)	18574	2,2-dibutyl-5-(2-quinolinylmethoxy)-1,2,3,4-tetrahydro-1-naphthalenol		C₂₈H₃₅NO₂	详情	详情
(VIII)	18575	(2S)-2-methoxy-2-phenylethanoyl chloride		C₉H₉ClO₂	详情	详情
(IX)	18576	2,2-dibutyl-5-(2-quinolinylmethoxy)-1,2,3,4-tetrahydro-1-naphthalenyl (2S)-2-methoxy-2-phenylethanoate		C₃₇H₄₃NO₄	详情	详情
(X)	18577	(3R)-4-anilino-3-(methylamino)-1-butanol		C₁₁H₁₈N₂O	详情	详情
(XI)	18578	2-amino-1,1-diphenyl-1-pentanol		C₁₇H₂₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The oxidation of 5-methoxy-1-tetralone (I) with SeO2 gives 5-methoxy-1,2-naphthoquinone (II), which is cyclized with 2,3-diaminobenzoic acid (II) by means of HCl in refluxing ethanol to yield 4-methoxybenzo[a]phenazine-11-carboxylic acid (IV). Finally, this acid is converted into the target amide by its condensation with N1,N1,2(R)-trimethylethane-1,2-diamine (V) by means of CDI in DMF.

参考文献中间体

合成目标

【1】 Vicker, N.; Burgess, L.; Chuckowree, I.S.; et al.; Novel angular benzophenazines: Dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents. J Med Chem 2002, 45, 3, 721.
【2】 Vicker, N.; Folkes, A.J.; Wang, S.; Milton, J.; Denny, W.A. (Xenova Group plc); Benzo[a]phenazin-11-carboxamide derivs. and their use as joint inhibitors of topomerase I and II. WO 0146157 .

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)	18568	5-methoxy-3,4-dihydro-1(2H)-naphthalenone	33892-75-0	C₁₁H₁₂O₂	详情	详情
(II)	47913	5-methoxy-1,2-naphthalenedione		C₁₁H₈O₃	详情	详情
(III)	47914	2,3-diaminobenzoic acid		C₇H₈N₂O₂	详情	详情
(IV)	47915	4-methoxybenzo[a]phenazine-11-carboxylic acid		C₁₈H₁₂N₂O₃	详情	详情
(V)	47916	(2R)-N(1),N(1)-dimethyl-1,2-propanediamine; N-[(2R)-2-aminopropyl]-N,N-dimethylamine		C₅H₁₄N₂	详情	详情

Extended Information