tert-butyl 4-aminophenethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】18966

【品名】tert-butyl 4-aminophenethylcarbamate

【CA登记号】

【分子式】C₁₃H₂₀N₂O₂

【分子量】236.31408

【元素组成】C 66.07% H 8.53% N 11.85% O 13.54%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XI)

2) Alternatively, amine (VI) was selectively protected as the carbamate (XI) with di-tert-butyl dicarbonate. This compound was condensed with sulfonyl chloride (IX) and pyridine to afford sulfonamide (XII), and the Boc protecting group was then removed with trifluoroacetic acid to give the primary amine (XIII). Subsequent addition of (XIII) to epoxide (V) provided the phenoxypropanolamine (XIV), and the silyl group was finally eliminated with methanolic HCl.

参考文献中间体

合成目标

【1】 Weber, A.E.; Mathvink, R.J.; Perkins, L.; Hutchins, J.E.; Candelore, M.R.; Tota, L.; Strader, C.D.; Wyvratt, M.J.; Fisher, M.H.; Potent, selective benzenesulfonamide agonists of the human beta3 adrenergic receptor. Bioorg Med Chem Lett 1998, 8, 9, 1101.
【2】 Fisher, M.H.; Mathvink, R.J.; Ok, H.O.; Parmee, E.R.; Weber, A.E. (Merck & Co., Inc.); Substd. phenyl sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. CA 2114712; EP 0611003; JP 1995010827; US 5451677; WO 9418161 .

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)	18960	tert-butyl(dimethyl)[4-[(2S)oxiranylmethoxy]phenoxy]silane; tert-butyl(dimethyl)silyl 4-[(2S)oxiranylmethoxy]phenyl ether		C₁₅H₂₄O₃Si	详情	详情
(VI)	18961	4-(2-aminoethyl)aniline; 4-(2-aminoethyl)phenylamine	13472-00-9	C₈H₁₂N₂	详情	详情
(IX)	18964	4-bromobenzenesulfonyl chloride	98-58-8	C₆H₄BrClO₂S	详情	详情
(XI)	18966	tert-butyl 4-aminophenethylcarbamate		C₁₃H₂₀N₂O₂	详情	详情
(XII)	18967	tert-butyl 4-[[(4-bromophenyl)sulfonyl]amino]phenethylcarbamate		C₁₉H₂₃BrN₂O₄S	详情	详情
(XIII)	18968	N-[4-(2-aminoethyl)phenyl]-4-bromobenzenesulfonamide		C₁₄H₁₅BrN₂O₂S	详情	详情
(XIV)	18969	4-bromo-N-[4-(2-[[(2S)-3-(4-[[tert-butyl(dimethyl)silyl]oxy]phenoxy)-2-hydroxypropyl]amino]ethyl)phenyl]benzenesulfonamide		C₂₉H₃₉BrN₂O₅SSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

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.

参考文献中间体

合成目标

【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3

该中间体在本合成路线中的序号：(X)

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.

参考文献中间体

合成目标

【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

Extended Information