1-(tert-butyl)-4-piperidinone; N-(tert-butyl)-4-piperidinone -Drug Synthesis Database

【结构式】

【分子编号】24875

【品名】1-(tert-butyl)-4-piperidinone; N-(tert-butyl)-4-piperidinone

【CA登记号】

【分子式】C₉H₁₇NO

【分子量】155.24012

【元素组成】C 69.63% H 11.04% N 9.02% O 10.31%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

There are several synthetic pathways leading to title compound which are depicted in Scheme. Generally, 1-alkyl-4,4 diphenylpiperidines Iike budipine are accessible in a simple manner and with attractive yields by a regioselective reaction of piperidine derivatives such as (I), (II), (III) or, par ticularly, 3-aroyl-4-aryl-4-hydroxypiperidines (IV) with benzene under Friedel Crafts' conditions.

参考文献中间体

合成目标

【1】 Schaefer, H.; Eistetter, K.; Klosa, J.; Menge, H.G.; Hackmack, G.; 4,4-Diphenylpiperidines - A new class of potent central stimulants. 5th Intl Symp Med Chem (July 19-22, Paris) 1976, Abst 052.
【2】 Hackmack, S.H.; et al.; Synthesis physical-chemical properties and pharmacologically-oriented screening studies on budipine and related 4,4-diphenylpiperidines. Arzneim-Forsch Drug Res 1984, 34, 3, 233.
【3】 Shaefer, H.; et al. (Byk Gulden Lomberg Chemische Fabrik GmbH); Alkylsubstituierte piperidin-N-oxide, verfahren zu ihrer herstellung. Ihre verwendung und sie enthaltende Arzneimittel. DE 2825322 .
【4】 Koch, H.; Budipine. Drugs Fut 1985, 10, 8, 621.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	24874	methyl 1-(tert-butyl)-4-phenyl-4-piperidinecarboxylate	C₁₇H₂₅NO₂	详情	详情
(II)	24875	1-(tert-butyl)-4-piperidinone; N-(tert-butyl)-4-piperidinone	C₉H₁₇NO	详情	详情
(III)	24876	1-(tert-butyl)-4-phenyl-1,2,3,6-tetrahydropyridine	C₁₅H₂₁N	详情	详情
(IV)	24877	[1-(tert-butyl)-4-hydroxy-4-phenyl-3-piperidinyl](phenyl)methanone	C₂₂H₂₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Quaternization of 1-ethyl-4-piperidone (XIV) with methyl iodide provides the ammonium salt (XV) which, upon treatment with tert-butylamine and NaHCO3, gives rise to 1-tert-butyl-4-piperidone (XVI). The reaction of 1-tert-butyl-4-piperidone (XVI) firstly with LiN(SiMe3)2 and subsequently with N-(5-chloro-2-pyridyl) trifluoromethanesulfonimide [(Tf)2NPyr] in THF provides the enol triflate (XVII). Reaction of triflate (XVII) with hexamethylditin in the presence of palladium catalyst furnishes 1-tert-butyl-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridine (XVIII). Stille coupling between the quinazolinyl triflate (XIII) and the stannyl tetrahydropyridine (XVIII) produces adduct (XIX). Finally, hydrogenation of the tetrahydropyridine double bond of (XIX) using PtO2 as the catalyst leads to the target piperidinyl compound.

参考文献中间体

合成目标

【1】 Stelmach, J.E.; Liu, L.; Patel, S.B.; Pivnichny, J.V.; Scapin, G.; Singh, S.; Hop, C.E.C.A.; Wang, Z.; Strauss, J.R.; Cameron, P.M.; Nichols, E.A.; O'Keefe, S.J.; O'Neill, E.A.; Schmatz, D.M.; Schwartz, C.D.; Thompson, C.M.; Zaller, D.M.; Doherty, J.B.; Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase. Bioorg Med Chem Lett 2003, 13, 2, 277.
【2】 Doherty, J.B.; Rupprecht, K.M.; Goulet, J.L.; Chen, M.-H.; Bao, J.; Liu, L.; Miao, S.; Hunt, J.A.; Hong, X.; Stelmach, J.E.; Ruzek, R.D.; Wisnoski, D.D.; Natarajan, S.R. (Merck & Co., Inc.); (Halo-benzo carbonyl)heterocyclic fused phenyl p38 kinase inhibiting agents. EP 1345603; WO 0258695 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	63190	5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydro-7-quinazolinyl trifluoromethanesulfonate		C₂₁H₁₁Cl₃F₄N₂O₄S	详情	详情
(XIV)	28868	1-ethyl-4-piperidinone; N-ethyl-4-piperidinone	3612-18-8	C₇H₁₃NO	详情	详情
(XV)	51994	1-ethyl-1-methyl-4-oxopiperidinium iodide		C₈H₁₆INO	详情	详情
(XVI)	24875	1-(tert-butyl)-4-piperidinone; N-(tert-butyl)-4-piperidinone		C₉H₁₇NO	详情	详情
(XVII)	63191	1-(tert-butyl)-1,2,3,6-tetrahydro-4-pyridinyl trifluoromethanesulfonate		C₁₀H₁₆F₃NO₃S	详情	详情
(XVIII)	63192	1-(tert-butyl)-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridine		C₁₂H₂₅NSn	详情	详情
(XIX)	63193	7-[1-(tert-butyl)-1,2,3,6-tetrahydro-4-pyridinyl]-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-2(1H)-quinazolinone		C₂₉H₂₇Cl₃FN₃O	详情	详情

Extended Information