1-Acetyl-4-piperidinecarbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】13700

【品名】1-Acetyl-4-piperidinecarbonyl chloride

【CA登记号】

【分子式】C₈H₁₂ClNO₂

【分子量】189.64152

【元素组成】C 50.67% H 6.38% Cl 18.69% N 7.39% O 16.87%

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)

The Friedel-Crafts condensation of 1,3-difluorobenzene (I) with 1-acetylpiperidine-4-carbonyl chloride (II) by means of AlCl3 in dichloromethane gives 1-acetyl-4-(2,4-difluorobenzoyl)piperidine (III), which is hydrotyzed with refluxing 6N HCl to yield 4-(2,4-difluorobenzoyl)piperidine (IV). The reaction of (IV) with hydroxylamine in refluxing ethanol affords the corresponding oxime (V), which is cyclized by means of KOH in boiling water giving 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (VI). Finally, this compound is condensed with 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (VII) by means of K2CO3 and Kl in a variety of solvents.

参考文献中间体

合成目标

【1】 Kennis, L.E.J.; Vandenberk, J. (Janssen Pharmaceutica NV); Novel 1,2-benzisoxazol-3-yl and 1, 2-benzisothiazo. EP 0196132; ES 8705881; JP 1986221186; US 4804663 .
【2】 Diller, D.; Krochmal, B.; Dolitzky, B.-Z.; Aronhime, J. (Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA, Inc.); Preparation of risperidone. WO 0212200; WO 0214286 .
【3】 Castaner, J.; Prous, J.; Risperidone. Drugs Fut 1988, 13, 12, 1052.

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)	13095	m-Difluorobenzene; 1,3-Difluorobenzene	372-18-9	C₆H₄F₂	详情	详情
(II)	13700	1-Acetyl-4-piperidinecarbonyl chloride		C₈H₁₂ClNO₂	详情	详情
(III)	23040	1-[4-(2,4-difluorobenzoyl)-1-piperidinyl]-1-ethanone		C₁₄H₁₅F₂NO₂	详情	详情
(IV)	23041	(2,4-difluorophenyl)(4-piperidinyl)methanone		C₁₂H₁₃F₂NO	详情	详情
(V)	23042	(2,4-difluorophenyl)(4-piperidinyl)methanone oxime		C₁₂H₁₄F₂N₂O	详情	详情
(VI)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情
(VII)	23044	3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one	63234-80-0	C₁₁H₁₅ClN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The mesylation of aniline (I) with methanesulfonyl chloride gives the sulfonamide (II), which is condensed with 1-acetylpiperidine-4-carbonyl chloride (III) by means of AlCl3 in dichloromethane to give N-[4-(1-acetylpiperidin-4-ylcarbonyl)phenyl]methanesulfonamide (IV). Deacetylation of (IV) with HCl in water yields the piperidine (V), which is finally condensed with 2-methyl-6-vinylpyridine by means of sodium acetate in methanol - water. The same procedure has been performed with [14C]-labeled aniline in order to obtain [14C]-labeled E-4031.

参考文献中间体

合成目标

【1】 Oinuma, H.; Yamanaka, M.; Miyake, K.; Hoshiko, T.; Minami, N.; Shoji, T.; Daiku, Y.; Sawada, K.; Nomoto, K. (Eisai Co., Ltd.); Piperidine deriv., pharmaceutical compsn. containing the same and use. EP 0235752; US 4876262; US 4996215; US 5118689; US 5179095 .
【2】 Miyake, K.; Yamanaka, M.; Katoh, H.; Shino, M.; Hamano, S.; Nomoto, K.-I.; Oinuma, H.; Sawada, K.; 4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents. J Med Chem 1990, 33, 3, 903.
【3】 Shino, M.; Oinuma, H.; Hamano, S.; Miyake, K.; Yamanaka, M.; Synthesis of antiarrhythmic [phenyl-14C]4'-[(4-piperidyl)carbonyl]methanesulfonanilides. J Label Compd Radiopharm 1990, 28, 8, 921.
【4】 Castaner, J.; Prous, J.; E-4031. Drugs Fut 1992, 17, 6, 455.

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)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(II)	13699	N-Phenylmethanesulfonamide; N-Phenyl methanesulfonamide	1197-22-4	C₇H₉NO₂S	详情	详情
(III)	13700	1-Acetyl-4-piperidinecarbonyl chloride		C₈H₁₂ClNO₂	详情	详情
(IV)	13701	N-[4-[(1-Acetyl-4-piperidinyl)carbonyl]phenyl]methanesulfonamide		C₁₅H₂₀N₂O₄S	详情	详情
(V)	13702	N-[4-(4-Piperidinylcarbonyl)phenyl]methanesulfonamide		C₁₃H₁₈N₂O₃S	详情	详情
(VI)	13703	2-Methyl-6-vinylpyridine	1122-70-9	C₈H₉N	详情	详情

Extended Information