2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine -Drug Synthesis Database

【结构式】

【分子编号】17606

【品名】2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine

【CA登记号】

【分子式】C₁₄H₂₂N₂

【分子量】218.34216

【元素组成】C 77.01% H 10.16% N 12.83%

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：(V)

The reaction of methyl anthranilate (I) with tetrahydrofuran-2,4-dione (II) by means of HCl in ethanol gives 2-(5-oxo-2,5-dihydrofuran-3-ylamino)benzoic acid methyl ester (III), which is cyclized by means of polyphosphoric acid (PPA) at 130-140 C yielding the tricyclic hydroxyketone (IV). The condensation of (IV) with 4-(2-aminoethyl)-1-benzylpiperidine (V) in N-methyl-2-pyrrolidone by a Dean-Stark elimination of water affords 2-[2-(1-benzyl-piperidin-4-yl)ethyl]-9-hydroxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one (VI), which is finally methylated with diazomethane in methanol.

参考文献中间体

合成目标

【1】 Castañer, J.; Mucke, H.A.M.; T-82. Drugs Fut 1998, 23, 10, 1075-1077.
【2】 Hasegawa, H.; Isomae, K.; Kotsugai, T.; Shioiri, N.; Sekine, K.; Taido, N.; Sato, S.; Kuraishi, T. (SSP Co., Ltd.); Quinoline derivs.. EP 0481429; JP 1993009188; JP 1993279355; US 5190951; US 5240934; US 5300517 .

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)	11161	methyl 2-aminobenzoate; Methyl anthranilate	134-20-3	C₈H₉NO₂	详情	详情
(II)	17603	Tetronic acid; 2,4(3H,5H)-Furandione	4971-56-6	C₄H₄O₃	详情	详情
(III)	17604	methyl 2-[(5-oxo-2,5-dihydro-3-furanyl)amino]benzoate		C₁₂H₁₁NO₄	详情	详情
(IV)	17605	9-hydroxyfuro[3,4-b]quinolin-1(3H)-one		C₁₁H₇NO₃	详情	详情
(V)	17606	2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine		C₁₄H₂₂N₂	详情	详情
(VI)	17607	2-[2-(1-benzyl-4-piperidinyl)ethyl]-9-hydroxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one		C₂₅H₂₇N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 2-(1-benzyl-4-piperidinyl)ethyl amine (I) with phenyl isocyanate (II) provided the corresponding urea (III), which was debenzylated by hydrogenolysis over Pd/C to afford the secondary amine (IV). Subsequent Mannich reaction of (IV) with 4-chromanone (V) and paraformaldehyde produced the (chromanylmethyl)piperidine (VI). After ketone reduction of (IV) by means of NaBH4, the resulting alcohol (VII) was dehydrated in refluxing 6 N HCl to furnish the target chromene.

参考文献中间体

合成目标

【1】 Mayer, P.; et al.; Modulation of the benzodioxane heterocycle in a novel series of potent alpha2 adrenoceptor antagonists. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 112.
【2】 Vidaluc, J.-L.; Imberg, T.; Marien, M.; Briley, M. (Pierre Fabre Medicament); Novel benzodioxanes and 1-(2H)-benzopyranes, their preparation and their use as medicine. WO 9802435 .

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)	17606	2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine		C₁₄H₂₂N₂	详情	详情
(II)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情
(III)	25201	N-[2-(1-benzyl-4-piperidinyl)ethyl]-N'-phenylurea		C₂₁H₂₇N₃O	详情	详情
(IV)	25202	N-phenyl-N'-[2-(4-piperidinyl)ethyl]urea		C₁₄H₂₁N₃O	详情	详情
(V)	14461	2,3-Dihydro-4H-chromen-4-one; 4-Chromanone	491-37-2	C₉H₈O₂	详情	详情
(VI)	25203	N-(2-[1-[(4-oxo-3,4-dihydro-2H-chromen-3-yl)methyl]-4-piperidinyl]ethyl)-N'-phenylurea		C₂₄H₂₉N₃O₃	详情	详情
(VII)	25204	N-(2-[1-[(4-hydroxy-3,4-dihydro-2H-chromen-3-yl)methyl]-4-piperidinyl]ethyl)-N'-phenylurea		C₂₄H₃₁N₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Horner-Emmons reaction of 1-benzyl-4-piperidone (I) with diethyl cyanomethylphosphonate (II) in the presence of K2CO3 provided the piperidinilydeneacetonitrile (III). Reduction of the double bond of (III) with magnesium in MeOH yielded the saturated nitrile (IV), which was further reduced to amine (V) using LiAlH4. Treatment of 6-phenyl-3-pyridazinone (VI) with POCl3 gave the chloropyridazine (VII). This was coupled with diamine (V) in the presence of ammonium chloride in refluxing butanol to furnish the title pyridazinamine, which was finally converted to the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Rival, Y.M.; Bourguignon, J.-J.; Contreras, J.-M.; Chayer, S.; Wermuth, C.G.; Aminopyridazines as acetylcholinesterase inhibitors. J Med Chem 1999, 42, 4, 730.

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)	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
(II)	10045	Diethyl cyanomethylphosphonate	2537-48-6	C₆H₁₂NO₃P	详情	详情
(III)	31448	2-(1-benzyl-4-piperidinylidene)acetonitrile		C₁₄H₁₆N₂	详情	详情
(IV)	31449	2-(1-benzyl-4-piperidinyl)acetonitrile		C₁₄H₁₈N₂	详情	详情
(V)	17606	2-(1-benzyl-4-piperidinyl)-1-ethanamine; 2-(1-benzyl-4-piperidinyl)ethylamine		C₁₄H₂₂N₂	详情	详情
(VI)	31450	6-phenyl-3(2H)-pyridazinone		C₁₀H₈N₂O	详情	详情
(VII)	31451	3-chloro-6-phenylpyridazine		C₁₀H₇ClN₂	详情	详情

Extended Information