3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine -Drug Synthesis Database

【结构式】

【分子编号】18182

【品名】3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine

【CA登记号】

【分子式】C₂₀H₂₆N₂

【分子量】294.43992

【元素组成】C 81.59% H 8.9% N 9.51%

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：(V)

Treatment of a benzenic solution of 4-piperidone hydrate (I) with anhydrous AlCl3 provided 4,4-diphenylpiperidine (II). Then, conjugate addition of acrylonitrile (III) in the presence of triethylamine in ethanol gave the cyanoethylpiperidine (IV), which was reduced with borane in THF to afford the intermediate primary amine (V). Dihydropyridine (IX) was prepared by Hantzsch synthesis by condensation of 3-aminocrotonamide (VI), 4-nitrobenzaldehyde (VII) and cyanoethyl acetoacetate (VIII) in refluxing ethanol. Cyanoethyl ester was then cleaved with dilute KOH at 0 C to give acid (X), which was finally coupled with amine (V) by treatment with DEC to yield the target amide.

参考文献中间体

合成目标

【1】 Cox, E.D.; et al.; Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate. J Med Chem 1998, 41, 14, 2643.

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)	18178	4,4-piperidinediol	73390-11-1	C₅H₁₁NO₂	详情	详情
(II)	13154	4,4-Diphenylpiperidine		C₁₇H₁₉N	详情	详情
(III)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(IV)	18181	3-(4,4-diphenyl-1-piperidinyl)propanenitrile		C₂₀H₂₂N₂	详情	详情
(V)	18182	3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine		C₂₀H₂₆N₂	详情	详情
(VI)	18183	(E)-3-amino-2-butenamide		C₄H₈N₂O	详情	详情
(VII)	18184	4-Nitrobenzaldehyde	555-16-8	C₇H₅NO₃	详情	详情
(VIII)	13993	2-cyanoethyl 3-oxobutanoate		C₇H₉NO₃	详情	详情
(IX)	18186	2-cyanoethyl 5-(aminocarbonyl)-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate		C₁₈H₁₈N₄O₅	详情	详情
(X)	18187	5-(aminocarbonyl)-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid		C₁₅H₁₅N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Hantzsch condensation of the (azidoethoxy)ketoester (I) with the benzylidene ketoester (II) formed the protected dihydropyridine (III). Selective deprotection of the cyanoethyl ester under basic conditions provided carboxylic acid (IV), which was further converted to amide (V). Then, acid cleavage of the tert-butyl ester gave acid (VI). Coupling with the (aminopropyl)piperidine (VII) furnished the corresponding amide (VIII). Finally, the azido group was reduced to the target amine by means of trimethyl phosphine.

参考文献中间体

合成目标

【1】 Tyring, S.K.; Vander Straten, M.; Carrasco, D.; Tetrahedron Lett 1998, 39, 30, 5293-96.
【2】 Hong, X.; Nagarathnam, D.; Marzbadi, M.R.; et al.; Design and synthesis of novel dihydropyridine alpha-1A antagonists. Bioorg Med Chem Lett 1999, 9, 19, 2843.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	31725	tert-butyl 4-(2-azidoethoxy)-3-oxobutanoate	C₁₀H₁₇N₃O₄	详情	详情
(II)	31726	2-cyanoethyl (Z)-3-(4-nitrophenyl)-2-propionyl-2-propenoate	C₁₅H₁₄N₂O₅	详情	详情
(III)	31727	3-(tert-butyl) 5-(2-cyanoethyl) 2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate	C₂₅H₃₀N₆O₇	详情	详情
(IV)	31728	6-[(2-azidoethoxy)methyl]-5-(tert-butoxycarbonyl)-2-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid	C₂₂H₂₇N₅O₇	详情	详情
(V)	31729	tert-butyl 5-(aminocarbonyl)-2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylate	C₂₂H₂₈N₆O₆	详情	详情
(VI)	31730	5-(aminocarbonyl)-2-[(2-azidoethoxy)methyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid	C₁₈H₂₀N₆O₆	详情	详情
(VII)	18182	3-(4,4-diphenyl-1-piperidinyl)-1-propanamine; 3-(4,4-diphenyl-1-piperidinyl)propylamine	C₂₀H₂₆N₂	详情	详情
(VIII)	31731	2-[(2-azidoethoxy)methyl]-N(3)-[3-(4,4-diphenyl-1-piperidinyl)propyl]-6-ethyl-4-(4-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxamide	C₃₈H₄₄N₈O₅	详情	详情

Extended Information