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【结 构 式】 
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【分子编号】26321 【品名】tert-butyl 2-(5-hydroxy-1H-indol-3-yl)ethylcarbamate 【CA登记号】 |
【 分 子 式 】C15H20N2O3 【 分 子 量 】276.33548 【元素组成】C 65.2% H 7.3% N 10.14% O 17.37% |
合成路线1
该中间体在本合成路线中的序号：(V)F-11356 is easily synthesized from serotonin following two synthetic pathways. The first method involves the preparation of 2-[3-[2-[N-(tert-butoxycarbonyl)amino]ethyl]-1H-indol-5-yloxy]acetic acid, which is obtained by protection of serotonin with BOC2O/NaOH, followed by O-alkylation with methyl bromoacetate and saponification of the methyl ester with KOH. The overall yield for the three steps was 81%. A coupling reaction between this acid and a phenyl piperazine derivative afforded the N-BOC-protected desired products which, upon subsequent treatment with trifluoroacetic anhydride, gave the free amines. In the second method, the phenylpiperazine derivatives were first treated with chloroacetylchloride and then the intermediates were allowed to react with N-BOC-serotonin to give the N-BOC-protected desired products. At this stage, and before the final deprotection, the R group can be modified to afford other analogues.
| 【1】 Perez, M.; John, G.W.; Colpaert, F.C.; Pauwels, P.J.; Halazy, S.; F-11356. Drugs Fut 1999, 24, 6, 605. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIIa) | 26319 | 4-(1-piperazinyl)benzonitrile | C11H13N3 | 详情 | 详情 | |
| (IVa) | 26320 | 4-[4-(2-chloroacetyl)-1-piperazinyl]benzonitrile | C13H14ClN3O | 详情 | 详情 | |
| (VIa) | 26322 | tert-butyl 2-(5-[2-[4-(4-cyanophenyl)-1-piperazinyl]-2-oxoethoxy]-1H-indol-3-yl)ethylcarbamate | C28H33N5O4 | 详情 | 详情 | |
| (I) | 26317 | 3-(2-Aminoethyl)-5-hydroxyindole; 5-Hydroxytryptamine; 3-(2-Aminoethyl)-1H-indol-5-ol | 50-67-9 | C10H12N2O | 详情 | 详情 |
| (II) | 26318 | 2-[(3-[2-[(tert-butoxycarbonyl)amino]ethyl]-1H-indol-5-yl)oxy]acetic acid | C17H22N2O5 | 详情 | 详情 | |
| (V) | 26321 | tert-butyl 2-(5-hydroxy-1H-indol-3-yl)ethylcarbamate | C15H20N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The protection of the 3-(2-aminoethyl)-1H-indol-5-ol (I) with di-tert-butyl dicarbonate gives the corresponding carbamate (II), which is condensed with the chloroacetyl piperazine (III) (obtained by reaction of 4-(1-piperazinyl) benzonitrile (IV) with chloroacetyl chloride (V) by means of CaCO3) using K2CO3 and KI in refluxing 2-butanone to yield the protected target compound (V). Finally, this compound is deprotected with TFA in toluene.
| 【1】 Halazy, S.; Perez, M.; Briley, M.; Pauwels, P. (Pierre Fabre Medicament); Indole-derived azylpiperazines as ligands for 5HT1-like receptors 5HT1B and 5HT1D. EP 0729455; FR 2712591; JP 1997505072; US 5726177; WO 9514004 . |
| 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) | 26317 | 3-(2-Aminoethyl)-5-hydroxyindole; 5-Hydroxytryptamine; 3-(2-Aminoethyl)-1H-indol-5-ol | 50-67-9 | C10H12N2O | 详情 | 详情 |
| (II) | 26321 | tert-butyl 2-(5-hydroxy-1H-indol-3-yl)ethylcarbamate | C15H20N2O3 | 详情 | 详情 | |
| (III) | 26319 | 4-(1-piperazinyl)benzonitrile | C11H13N3 | 详情 | 详情 | |
| (IV) | 26320 | 4-[4-(2-chloroacetyl)-1-piperazinyl]benzonitrile | C13H14ClN3O | 详情 | 详情 | |
| (V) | 26322 | tert-butyl 2-(5-[2-[4-(4-cyanophenyl)-1-piperazinyl]-2-oxoethoxy]-1H-indol-3-yl)ethylcarbamate | C28H33N5O4 | 详情 | 详情 | |
| (VI) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |