【结 构 式】 |
【分子编号】29271 【品名】2-[2-[5-(tert-butyl)-1H-indol-3-yl]ethyl]-1H-isoindole-1,3(2H)-dione 【CA登记号】 |
【 分 子 式 】C22H22N2O2 【 分 子 量 】346.42896 【元素组成】C 76.28% H 6.4% N 8.09% O 9.24% |
合成路线1
该中间体在本合成路线中的序号:(IX)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.
【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:(VIII)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 the target tryptamine. In an alternative procedure, 4-phthalimidobutyraldehyde diethyl acetal (VII) was prepared by treatment of amine (V) with N-carbethoxyphthalimide (VI). Fisher reaction of (VII) with hydrazine (II) produced the (phthalimidoethyl)indole (VIII), which was deprotected with hydrazine to furnish the corresponding tryptamine.
【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) | 23323 | 4,4-diethoxybutylamine; 4,4-diethoxy-1-butanamine | 6346-09-4 | C8H19NO2 | 详情 | 详情 |
(VI) | 10283 | ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide | 22509-74-6 | C11H9NO4 | 详情 | 详情 |
(VII) | 23325 | 2-(4,4-diethoxybutyl)-1H-isoindole-1,3(2H)-dione | C16H21NO4 | 详情 | 详情 | |
(VIII) | 29271 | 2-[2-[5-(tert-butyl)-1H-indol-3-yl]ethyl]-1H-isoindole-1,3(2H)-dione | C22H22N2O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(IX)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.
【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 |