2-[5-(tert-butyl)-1H-indol-3-yl]-1-ethanamine -Drug Synthesis Database

【结构式】

【分子编号】29270

【品名】2-[5-(tert-butyl)-1H-indol-3-yl]-1-ethanamine

【CA登记号】

【分子式】C₁₄H₂₀N₂

【分子量】216.32628

【元素组成】C 77.73% H 9.32% N 12.95%

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：(V)

Diazotization of 4-tert-butylaniline (I) with NaNO2 and HCl, followed by reduction of the resulting diazonium salt with SnCl2 provided hydrazine (II). Fisher indolization with 4-chlorobutyraldehyde (IV), (obtained by hydrogenation of acid chloride (III)), then afforded tryptamine (V). In an alternative procedure, 4-phthalimidobutyraldehyde diethyl acetal (VIII) was prepared by treatment of amine (VI) with N-carbethoxyphthalimide (VII). Fisher reaction of (VII) with hydrazine (II) produced the (phthalimidoethyl)indole (IX), which was deprotected with hydrazine to furnish the corresponding tryptamine (V). Subsequent condensation of (V) with di-tert-butyl dicarbonate gave carbamate (X). This was finally reduced by means of LiAlH4 providing the target N-methyl tryptamine.

参考文献中间体

合成目标

【1】 Xu, Y.-C.; Schaus, J.M.; Walker, C.; Krushinski, J.; Adhamm, N.; Zgombick, J.M.; Liang, S.X.; Kohlman, D.T.; Audia, J.E.; N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem 1999, 42, 3, 526.
【2】 Audia, J.E.; Cohen, M.L.; Gidda, J.S.; Nelson, D.L.G.; Baker, S.R.; Ezquerra-Carrera, J.; Lamas-Peteira, C.; Pedregal-Tercero, C. (Eli Lilly and Company); Method for treating 5HT2B receptor related conditions. EP 0749313; JP 1997510216; US 5663178; WO 9524200; WO 9624351 .
【3】 Audia, J.E.; et al. (Eli Lilly and Company); Intermediates to tetrahydro-beta-carbolines. US 5635528 .

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)	27492	4-(tert-butyl)aniline	769-92-6	C₁₀H₁₅N	详情	详情
(II)	29269	1-[4-(tert-butyl)phenyl]hydrazine		C₁₀H₁₆N₂	详情	详情
(III)	11265	4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride	4635-59-0	C₄H₆Cl₂O	详情	详情
(IV)	23428	4-Chlorobutanal		C₄H₇ClO	详情	详情
(V)	29270	2-[5-(tert-butyl)-1H-indol-3-yl]-1-ethanamine		C₁₄H₂₀N₂	详情	详情
(VI)	23323	4,4-diethoxybutylamine; 4,4-diethoxy-1-butanamine	6346-09-4	C₈H₁₉NO₂	详情	详情
(VII)	10283	ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide	22509-74-6	C₁₁H₉NO₄	详情	详情
(VIII)	23325	2-(4,4-diethoxybutyl)-1H-isoindole-1,3(2H)-dione		C₁₆H₂₁NO₄	详情	详情
(IX)	29271	2-[2-[5-(tert-butyl)-1H-indol-3-yl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₂N₂O₂	详情	详情
(X)	29272	tert-butyl 2-[5-(tert-butyl)-1H-indol-3-yl]ethylcarbamate		C₁₉H₂₈N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Diazotization of 4-tert-butylaniline (I) with NaNO2 and HCl, followed by reduction of the resulting diazonium salt with SnCl2 provided hydrazine (II). Fisher indolization with 4-chlorobutyraldehyde (IV), (obtained by hydrogenation of acid chloride (III)), then afforded tryptamine (V). In an alternative procedure, 4-phthalimidobutyraldehyde diethyl acetal (VIII) was prepared by treatment of amine (VI) with N-carbethoxyphthalimide (VII). Fisher reaction of (VII) with hydrazine (II) produced the (phthalimidoethyl)indole (IX), which was deprotected with hydrazine to furnish the corresponding tryptamine (V). Finally, dimethylation of (V) by means of methyl methanesulfonate provided the target N,N-dimethyl tryptamine.

参考文献中间体

合成目标

【1】 Xu, Y.-C.; Schaus, J.M.; Walker, C.; Krushinski, J.; Adhamm, N.; Zgombick, J.M.; Liang, S.X.; Kohlman, D.T.; Audia, J.E.; N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem 1999, 42, 3, 526.
【2】 Audia, J.E.; Cohen, M.L.; Gidda, J.S.; Nelson, D.L.G.; Baker, S.R.; Ezquerra-Carrera, J.; Lamas-Peteira, C.; Pedregal-Tercero, C. (Eli Lilly and Company); Method for treating 5HT2B receptor related conditions. EP 0749313; JP 1997510216; US 5663178; WO 9524200; WO 9624351 .
【3】 Audia, J.E.; et al. (Eli Lilly and Company); Intermediates to tetrahydro-beta-carbolines. US 5635528 .

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)	27492	4-(tert-butyl)aniline	769-92-6	C₁₀H₁₅N	详情	详情
(II)	29269	1-[4-(tert-butyl)phenyl]hydrazine		C₁₀H₁₆N₂	详情	详情
(III)	11265	4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride	4635-59-0	C₄H₆Cl₂O	详情	详情
(IV)	23428	4-Chlorobutanal		C₄H₇ClO	详情	详情
(V)	29270	2-[5-(tert-butyl)-1H-indol-3-yl]-1-ethanamine		C₁₄H₂₀N₂	详情	详情
(VI)	23323	4,4-diethoxybutylamine; 4,4-diethoxy-1-butanamine	6346-09-4	C₈H₁₉NO₂	详情	详情
(VII)	10283	ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide	22509-74-6	C₁₁H₉NO₄	详情	详情
(VIII)	23325	2-(4,4-diethoxybutyl)-1H-isoindole-1,3(2H)-dione		C₁₆H₂₁NO₄	详情	详情
(IX)	29271	2-[2-[5-(tert-butyl)-1H-indol-3-yl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₂N₂O₂	详情	详情

Extended Information