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【结 构 式】 
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【分子编号】21897 【品名】2-(4-benzhydryl-1-piperazinyl)ethyl 3-oxobutanoate 【CA登记号】 |
【 分 子 式 】C23H28N2O3 【 分 子 量 】380.487 【元素组成】C 72.61% H 7.42% N 7.36% O 12.61% |
合成路线1
该中间体在本合成路线中的序号：(V)1) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III), which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V). The condensation of (V) with 3-nitrobenzaldehyde (VI) gives the intermediate benzylidene derivative (VII), which is finally cyclized with methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
| 【1】 Meguro, K.; Kawamatsu, Y.; Aizawa, M.; Nagaoka, A.; Sohda, T.; New 1,4-dihydropyridine derivatives with potent an. Chem Pharm Bull 1985, 33, 9, 3787. |
| 【2】 Meguro, K.; Nagaoka, A. (Takeda Chemical Industries, Ltd.); Dihydropyridine derivs., their production and use. EP 0138505; JP 1985084269; US 4603135 . |
| 【3】 Prous, J.; Castaner, J.; CV-4093. Drugs Fut 1988, 13, 3, 207. |
| 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) | 21893 | 2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine | 103-76-4 | C6H14N2O | 详情 | 详情 |
| (II) | 12079 | Bromodiphenylmethane; 1-[Bromo(phenyl)methyl]benzene; Benzhydrylbromide | 776-74-9 | C13H11Br | 详情 | 详情 |
| (III) | 12674 | 2-(4-Benzhydryl-1-piperazinyl)-1-ethanol | C19H24N2O | 详情 | 详情 | |
| (IV) | 21896 | 4-methyl-2H-oxet-2-one | C4H4O2 | 详情 | 详情 | |
| (V) | 21897 | 2-(4-benzhydryl-1-piperazinyl)ethyl 3-oxobutanoate | C23H28N2O3 | 详情 | 详情 | |
| (VI) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (VII) | 21899 | 2-(4-benzhydryl-1-piperazinyl)ethyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C30H31N3O5 | 详情 | 详情 | |
| (VIII) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)2) The reaction of 2-(4-piperazinyl)ethanol (I) with diphenylmethyl bromide (II) by means of K2CO3 in DMF gives 2-[4-(diphenylmethyl)-1-piperazinyl] ethanol (III), which is condensed with diketene (IV) at 80 C to yield 2-[4-(diphenylmethyl)-1-piperazinyl] ethyl acetoacetate (V). The reaction of acetoacetate (V) with NH3 in ethanol gives the corresponding aminocrotonate (IX), which is then cyclized with methyl (3-nitrobenzylidene)acetoacetate (VI) [prepared from methyl acetoacetate (X) and 3-nitrobenzaldehyde (VI)] in refluxing isopropanol.
| 【1】 Meguro, K.; Kawamatsu, Y.; Aizawa, M.; Nagaoka, A.; Sohda, T.; New 1,4-dihydropyridine derivatives with potent an. Chem Pharm Bull 1985, 33, 9, 3787. |
| 【2】 Meguro, K.; Nagaoka, A. (Takeda Chemical Industries, Ltd.); Dihydropyridine derivs., their production and use. EP 0138505; JP 1985084269; US 4603135 . |
| 【3】 Prous, J.; Castaner, J.; CV-4093. Drugs Fut 1988, 13, 3, 207. |
| 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) | 21893 | 2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine | 103-76-4 | C6H14N2O | 详情 | 详情 |
| (II) | 12079 | Bromodiphenylmethane; 1-[Bromo(phenyl)methyl]benzene; Benzhydrylbromide | 776-74-9 | C13H11Br | 详情 | 详情 |
| (III) | 12674 | 2-(4-Benzhydryl-1-piperazinyl)-1-ethanol | C19H24N2O | 详情 | 详情 | |
| (IV) | 21896 | 4-methyl-2H-oxet-2-one | C4H4O2 | 详情 | 详情 | |
| (V) | 21897 | 2-(4-benzhydryl-1-piperazinyl)ethyl 3-oxobutanoate | C23H28N2O3 | 详情 | 详情 | |
| (VI) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (IX) | 21900 | 2-(4-benzhydryl-1-piperazinyl)ethyl (E)-3-amino-2-butenoate | C23H29N3O2 | 详情 | 详情 | |
| (X) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (XI) | 12276 | methyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C12H11NO5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)3) By cyclization of acetoacetate (V) with aldehyde (VI) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol.
| 【1】 Meguro, K.; Kawamatsu, Y.; Aizawa, M.; Nagaoka, A.; Sohda, T.; New 1,4-dihydropyridine derivatives with potent an. Chem Pharm Bull 1985, 33, 9, 3787. |
| 【2】 Meguro, K.; Nagaoka, A. (Takeda Chemical Industries, Ltd.); Dihydropyridine derivs., their production and use. EP 0138505; JP 1985084269; US 4603135 . |
| 【3】 Prous, J.; Castaner, J.; CV-4093. Drugs Fut 1988, 13, 3, 207. |