ethyl 4-(2-aminophenoxy)butanoate -Drug Synthesis Database

【结构式】

【分子编号】21940

【品名】ethyl 4-(2-aminophenoxy)butanoate

【CA登记号】

【分子式】C₁₂H₁₇NO₃

【分子量】223.27192

【元素组成】C 64.55% H 7.67% N 6.27% O 21.5%

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：(V)

Reduction of ketoester (I) with NaBH4 in THF-MeOH afforded diol (II), which was treated with HCl in toluene to give chlorohydrin (III). Benzanilide (VII) was prepared by condensation of acid chloride (IV) with aniline (V), followed by catalytic hydrogenolysis of the resulting benzyl ether (VI). Then, alkylation of phenol (VII) with chloride (III) in the presence of K2CO3 provided ether (VIII). The hydroxyl group of (VIII) was converted to bromide (IX) using CBr4 and this compound was condensed with N-(2-methoxyphenyl)piperazine (X) to produce disubstituted piperazine (XI). The ethyl ester group of (XI) was finally hydrolyzed using KOH in aqueous EtOH.

参考文献中间体

合成目标

【1】 Yoshida, K.; Horikoshi, Y.; Eta, M.; Chikazawa, J.; Ogishima, M.; Fukuda, Y.; Sato, H.; Synthesis of benzanilide derivatives as dual actin. Bioorg Med Chem Lett 1998, 8, 21, 2967.

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)	23231	methyl 3-(4-methylphenyl)-3-oxopropanoate		C₁₁H₁₂O₃	详情	详情
(II)	23232	1-(4-methylphenyl)-1,3-propanediol		C₁₀H₁₄O₂	详情	详情
(III)	23233	3-chloro-3-(4-methylphenyl)-1-propanol		C₁₀H₁₃ClO	详情	详情
(IV)	23234	4-(benzyloxy)benzoyl chloride		C₁₄H₁₁ClO₂	详情	详情
(V)	21940	ethyl 4-(2-aminophenoxy)butanoate		C₁₂H₁₇NO₃	详情	详情
(VI)	23236	ethyl 4-(2-[[4-(benzyloxy)benzoyl]amino]phenoxy)butanoate		C₂₆H₂₇NO₅	详情	详情
(VII)	23237	ethyl 4-[2-[(4-hydroxybenzoyl)amino]phenoxy]butanoate		C₁₉H₂₁NO₅	详情	详情
(VIII)	23238	ethyl 4-[2-([4-[3-hydroxy-1-(4-methylphenyl)propoxy]benzoyl]amino)phenoxy]butanoate		C₂₉H₃₃NO₆	详情	详情
(IX)	23239	ethyl 4-[2-([4-[3-bromo-1-(4-methylphenyl)propoxy]benzoyl]amino)phenoxy]butanoate		C₂₉H₃₂BrNO₅	详情	详情
(X)	11882	1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine	35386-24-4	C₁₁H₁₆N₂O	详情	详情
(XI)	23241	ethyl 4-[2-([4-[3-[4-(2-methoxyphenyl)-1-piperazinyl]-1-(4-methylphenyl)propoxy]benzoyl]amino)phenoxy]butanoate		C₄₀H₄₇N₃O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The condensation of methyl 4-chloro-3-nitrobenzoate (I) with dipropylbenzhydryl amine (II), followed by reduction of the nitro group of the resulting (III) with H2 in the presence of PtO2 yielded diamine (IV). Treatment of (IV) with triethyl orthoformate and formic acid at 120 C produced the benzimidazole (V), which was hydrolyzed with NaOH to the benzimidazolecarboxylic (VI). Finally, acid (VI) was condensed with aniline (VII) using 2-chloro-1-methylpyridinium iodide (CMP) and Bu3N to furnish the target amide.

参考文献中间体

合成目标

【1】 Takami, H.; Kishibayashi, N.; Ishii, A.; Kumazawa, T.; Indole and benzimidazole derivatives as steroid 5alpha-reductase inhibitors in the rat prostate. Bioorg Med Chem 1998, 6, 12, 2441.

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)	21934	methyl 4-chloro-3-nitrobenzoate	14719-83-6	C₈H₆ClNO₄	详情	详情
(II)	21935	bis(4-propylphenyl)methanamine; bis(4-propylphenyl)methylamine		C₁₉H₂₅N	详情	详情
(III)	21936	N-[4-(methoxymethyl)-2-nitrophenyl]-N-[phenyl(4-propylphenyl)methyl]amine; 4-(methoxymethyl)-2-nitro-N-[phenyl(4-propylphenyl)methyl]aniline		C₂₄H₂₆N₂O₃	详情	详情
(IV)	21937	methyl 3-amino-4-[[bis(4-propylphenyl)methyl]amino]benzoate		C₂₇H₃₂N₂O₂	详情	详情
(V)	21938	methyl 1-[bis(4-propylphenyl)methyl]-1H-benzimidazole-5-carboxylate		C₂₈H₃₀N₂O₂	详情	详情
(VI)	21939	1-[bis(4-propylphenyl)methyl]-1H-benzimidazole-5-carboxylic acid		C₂₇H₂₈N₂O₂	详情	详情
(VII)	21940	ethyl 4-(2-aminophenoxy)butanoate		C₁₂H₁₇NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

Imidazole-5-carboxylic acid (VIII) was condensed with the aniline (VII) using 2-chloro-1-methylpyridinium iodide (CMP) and Bu3N to afford amide (XI). Subsequent alkylation of the indole nitrogen atom of (XI) with 4,4'-dipropylbenzhydryl bromide (IX) in the presence of t-BuOK provided the target compound.

参考文献中间体

合成目标

【1】 Takami, H.; Kishibayashi, N.; Ishii, A.; Kumazawa, T.; Indole and benzimidazole derivatives as steroid 5alpha-reductase inhibitors in the rat prostate. Bioorg Med Chem 1998, 6, 12, 2441.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	21940	ethyl 4-(2-aminophenoxy)butanoate		C₁₂H₁₇NO₃	详情	详情
(VIII)	21941	1H-benzimidazole-5-carboxylic acid	15788-16-6	C₈H₆N₂O₂	详情	详情
(IX)	21942	1-[bromo(4-propylphenyl)methyl]-4-propylbenzene		C₁₉H₂₃Br	详情	详情
(XI)	21944	ethyl 4-[2-[(1H-indol-5-ylcarbonyl)amino]phenoxy]butanoate		C₂₁H₂₂N₂O₄	详情	详情

Extended Information