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【结 构 式】 
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【分子编号】52065 【品名】tert-butyl 4-[(1-benzyl-4-piperidinyl)amino]phenethylcarbamate 【CA登记号】 |
【 分 子 式 】C25H35N3O2 【 分 子 量 】409.57192 【元素组成】C 73.31% H 8.61% N 10.26% O 7.81% |
合成路线1
该中间体在本合成路线中的序号：(IX)The aliphatic amino group of 4-aminophenethylamine (VI) was regioselectively protected as the N-Boc derivative (VII) using Boc2O. Subsequent reductive alkylation of aniline (VII) with N-benzyl-4-piperidone (VIII) afforded the anilinopiperidine (IX). The N-benzyl group of (IX) was then removed by transfer hydrogenolysis, and the resulting piperidine (X) was condensed with octyl isocyanate (XI), yielding the corresponding urea (XII). After acidic cleavage of the N-Boc protecting group of (XII), the primary amine (XIII) was condensed with the intermediate epoxide (V) to produce the amino alcohol (XIV). Final desilylation of (XIV) gave rise to the title compound.
| 【1】 Solvibile, W.R.; et al.; Potent, selective agonists of the human beta3-adrenergic receptor. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 35. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 52064 | tert-butyl[4-[(2S)oxiranylmethoxy]phenoxy]diphenylsilane; tert-butyl(diphenyl)silyl 4-[(2S)oxiranylmethoxy]phenyl ether | C25H28O3Si | 详情 | 详情 | |
| (VI) | 18961 | 4-(2-aminoethyl)aniline; 4-(2-aminoethyl)phenylamine | 13472-00-9 | C8H12N2 | 详情 | 详情 |
| (VII) | 18966 | tert-butyl 4-aminophenethylcarbamate | C13H20N2O2 | 详情 | 详情 | |
| (VIII) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (IX) | 52065 | tert-butyl 4-[(1-benzyl-4-piperidinyl)amino]phenethylcarbamate | C25H35N3O2 | 详情 | 详情 | |
| (X) | 52066 | tert-butyl 4-(4-piperidinylamino)phenethylcarbamate | C18H29N3O2 | 详情 | 详情 | |
| (XI) | 52067 | 1-isocyanatooctane; octyl isocyanate | C9H17NO | 详情 | 详情 | |
| (XII) | 52068 | tert-butyl 4-([1-[(octylamino)carbonyl]-4-piperidinyl]amino)phenethylcarbamate | C27H46N4O3 | 详情 | 详情 | |
| (XIII) | 52069 | 4-[4-(2-aminoethyl)anilino]-N-octyl-1-piperidinecarboxamide | C22H38N4O | 详情 | 详情 | |
| (XIV) | 52070 | 4-[4-(2-[[(2S)-3-(4-[[tert-butyl(diphenyl)silyl]oxy]phenoxy)-2-hydroxypropyl]amino]ethyl)anilino]-N-octyl-1-piperidinecarboxamide | C47H66N4O4Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)4-Aminophenethylamine (IX) was selectively protected at the aliphatic amino group by means of Boc2O to afford (X). Reductive alkylation of aniline (X) with N-benzyl-4-piperidone (XI) in the presence of NaBH(OAc)3 furnished the secondary amine (XII). Subsequent N-benzyl group cleavage in (XI) by transfer hydrogenolysis gave rise to diamine (XIII), which was further converted to urea (XV) by coupling with isocyanate (XIV). The N-Boc group of (XV) was then cleaved by means of formic acid, yielding amine (XVI). The title compound was then obtained by condensation of amine (XVI) with epoxide (VIII), followed by removal of the N-Boc and silyl protecting groups.
| 【1】 Mulvey, R.; Ashwell, M.A.; Solvibile, W.R. Jr.; Han, S.; Tillet, J.; Largis, E.; 4-Aminopiperidine ureas as potent selective agonists of the human beta3-adrenergic receptor. Bioorg Med Chem Lett 2001, 11, 24, 3123. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 59665 | tert-butyl 2-{[tert-butyl(diphenyl)silyl]oxy}-5-[(2S)oxiranylmethoxy]phenyl(methylsulfonyl)carbamate | C31H39NO7SSi | 详情 | 详情 | |
| (IX) | 18961 | 4-(2-aminoethyl)aniline; 4-(2-aminoethyl)phenylamine | 13472-00-9 | C8H12N2 | 详情 | 详情 |
| (X) | 18966 | tert-butyl 4-aminophenethylcarbamate | C13H20N2O2 | 详情 | 详情 | |
| (XI) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (XII) | 52065 | tert-butyl 4-[(1-benzyl-4-piperidinyl)amino]phenethylcarbamate | C25H35N3O2 | 详情 | 详情 | |
| (XIII) | 52066 | tert-butyl 4-(4-piperidinylamino)phenethylcarbamate | C18H29N3O2 | 详情 | 详情 | |
| (XIV) | 59666 | 1,4-difluoro-2-(isocyanatomethyl)benzene; 2,5-difluorobenzyl isocyanate | C8H5F2NO | 详情 | 详情 | |
| (XV) | 59667 | tert-butyl 4-[(1-{[(2,5-difluorobenzyl)amino]carbonyl}-4-piperidinyl)amino]phenethylcarbamate | C26H34F2N4O3 | 详情 | 详情 | |
| (XVI) | 59668 | 4-[4-(2-aminoethyl)anilino]-N-(2,5-difluorobenzyl)-1-piperidinecarboxamide | C21H26F2N4O | 详情 | 详情 |