1-benzyl-4-piperidinecarbonitrile -Drug Synthesis Database

【结构式】

【分子编号】29013

【品名】1-benzyl-4-piperidinecarbonitrile

【CA登记号】

【分子式】C₁₃H₁₆N₂

【分子量】200.28352

【元素组成】C 77.96% H 8.05% N 13.99%

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：(VI)

By condensation of 4-(4-fluorobenzoyl)piperidine (IX) with 6-(2-bromo ethyl)-7-methyl-2,3-dihydro-5H-thiazolo[2,3-a]pyrimidin-5-one (IV) by means of Na2CO3 in refluxing 4-methyl-2-pentanone. The starting products are obtained as follows: The cyclization of 4-hydroxy-5-(2-hydroxyethyl)-6-methyl-2-mercaptopyrimidine (I) with 1,2-dibromo ethane (II) by means of K2CO3 in hot dimethylacetamide gives 2,3-dihydro-6-(2-hydroxyethyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (II), which by reaction with HBr in refluxing acetic acid is converted to the corresponding 6-(2-bromoethyl) derivative (IV). The Grignard reaction of 4-bromofluorobenzene (V) with N benzyl-4 cyanopiperidine (VI) by means of Mg in dimethoxyethane gives 4-(4-fluorobenzoyl)-N-benzylpiperidine (VII), which is treated with ethyl chlorocarbo-nate in refluxing toluene to afford ethyl 4-(4-fluorobenzoyl)piperidine-1-carboxylate (VIII). Finally, this compound is treated with HBr in refluxing 48% HBr to give (IX).

参考文献中间体

合成目标

【1】 Kennis, L.; Mertens, J.C. (Janssen Pharmaceutica NV); Bicyclic pyrimidin-5-one derivatives. DD 215553; EP 0070053; US 4443451 .
【2】 Serradell, M.N.; Castaner, J.; Setoperone. Drugs Fut 1985, 10, 1, 40.

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)	29009	5-(2-hydroxyethyl)-6-methyl-2-sulfanyl-4-pyrimidinol		C₇H₁₀N₂O₂S	详情	详情
(II)	10252	1,2-Dibromoethane; Ethylene dibromide	106-93-4	C₂H₄Br₂	详情	详情
(III)	29010	6-(2-hydroxyethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one		C₉H₁₂N₂O₂S	详情	详情
(IV)	29011	6-(2-bromoethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one		C₉H₁₁BrN₂OS	详情	详情
(V)	29012	1-bromo-4-fluorobenzene	460-00-4	C₆H₄BrF	详情	详情
(VI)	29013	1-benzyl-4-piperidinecarbonitrile		C₁₃H₁₆N₂	详情	详情
(VII)	29014	(1-benzyl-4-piperidinyl)(4-fluorophenyl)methanone		C₁₉H₂₀FNO	详情	详情
(VIII)	29015	ethyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate		C₁₅H₁₈FNO₃	详情	详情
(IX)	21497	(4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine	56346-57-7	C₁₂H₁₄FNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

By reaction of 4-(p-fluorobenzoyl)piperidine (I) with 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (II) by means of Na2CO3 in refluxing 4-methyl-2-pentanone. The starting compounds are prepared as follows: 1) The Grignard reaction of N-benzyl-4-cyanopiperidine (III) with p-fluorophenylmagnesium bromide (IV) ethyl ether gives N-benzyl-4-p-fluorobenzoyl)piperidine (V), which by reaction with Na2CO3 and ethyl chloroformate (A) is converted into N-ethoxycarbonyl-4-(p-fluorobenzoyl)piperidine (VI). Finally, this compound is hydrolyzed with 48% HBr to give (I). 2) The reaction of ethyl anthranilate (VII) with ethyl chloroformate (A) in refluxing xylene gives ethyl 2-(ethoxycarbonylamino)benzoate (VIII), which is cyclized with 2-aminoethanol (B) at 170 C to afford 3-(2-hydroxyethyl)-2,4-(1H,3H)-quinazolinedione (IX). Finally, this compound is treated with SOCl2 in refluxing chloroform to afford (II).

参考文献中间体

合成目标

【1】 Van Der, M.; Keninis, L.; Vandenberk, J.; Van Heertum, A. (Janssen Pharmaceutica NV); Piperidinylalkyl quinazoline compounds, composition and method of use. EP 0013612; JP 55105679; US 4335127 .
【2】 Blancafort, P.; Paton, D.M.; Serradell, M.N.; Castaner, J.; Ketanserin. Drugs Fut 1981, 6, 11, 684.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(B)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(I)	21497	(4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine	56346-57-7	C₁₂H₁₄FNO	详情	详情
(II)	32277	3-(2-chloroethyl)-2,4(1H,3H)-quinazolinedione	5081-87-8	C₁₀H₉ClN₂O₂	详情	详情
(III)	29013	1-benzyl-4-piperidinecarbonitrile		C₁₃H₁₆N₂	详情	详情
(IV)	13643	4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide	352-13-6	C₆H₄BrFMg	详情	详情
(V)	29014	(1-benzyl-4-piperidinyl)(4-fluorophenyl)methanone		C₁₉H₂₀FNO	详情	详情
(VI)	29015	ethyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate		C₁₅H₁₈FNO₃	详情	详情
(VII)	32278	ethyl 2-aminobenzoate	87-25-2	C₉H₁₁NO₂	详情	详情
(VIII)	32279	ethyl 2-[(ethoxycarbonyl)amino]benzoate		C₁₂H₁₅NO₄	详情	详情
(IX)	32280	3-(2-hydroxyethyl)-2,4(1H,3H)-quinazolinedione		C₁₀H₁₀N₂O₃	详情	详情

Extended Information