N-(1-benzyl-4-piperidinyl)-5-chloropentanamide -Drug Synthesis Database

【结构式】

【分子编号】44278

【品名】N-(1-benzyl-4-piperidinyl)-5-chloropentanamide

【CA登记号】

【分子式】C₁₇H₂₅ClN₂O

【分子量】308.85108

【元素组成】C 66.11% H 8.16% Cl 11.48% N 9.07% O 5.18%

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：(XII)

Acylation of 4-amino-1-benzylpiperidine (X) with 5-chloropentanoyl chloride (XI) gives the chloro amide (XII), which is further cyclized to the 2-piperidone (XIII) in the presence of NaH. Replacement of the N-benzyl (XIII) for a N-Boc (XIV) protecting group is then accomplished by catalytic hydrogenolysis in the presence of Boc2O (1,2). Alkylation of piperidone (XIV) with allyl bromide (XV) yields the racemic 3-allyl-2-piperidone (XVI), which is subjected to oxidative cleavage with RuO2/NaIO4, producing carboxylic acid (XVII). After coupling of acid (XVII) with methylamine, the resultant N-methyl amide (XVIII) is deprotected by treatment with trifluoroacetic acid to give piperidine (XIX)

参考文献中间体

合成目标

【1】 Ting, P.C.; Lee, J.F.; Shih, N.-Y.; et al.; Identification of a novel 1'-[5-((3,5-dichlorobenzoyl)methylamino)-3-(3,4-dichlorophenyl)-4-(methoxyimino)pentyl]- 2-oxo-(1,4'-bipiperidine) as a dual NK(1)/NK(2) antagonist. Bioog. Med. Chem. Lett. 2002, 12, 16, 2125.
【2】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	34809	N-benzoyl-N'-(1-benzyl-4-piperidinyl)urea		C₂₀H₂₃N₃O₂	详情	详情
(XI)	44277	5-chloropentanoyl chloride	1575-61-7	C₅H₈Cl₂O	详情	详情
(XII)	44278	N-(1-benzyl-4-piperidinyl)-5-chloropentanamide		C₁₇H₂₅ClN₂O	详情	详情
(XIII)	44279			C₁₇H₂₄N₂O	详情	详情
(XIV)	61361			C₁₅H₂₆N₂O₃	详情	详情
(XVI)	61362			C₁₈H₃₀N₂O₃	详情	详情
(XVII)	61352			C₁₇H₂₈N₂O₅	详情	详情
(XVIII)	61353			C₁₈H₃₁N₃O₄	详情	详情
(XIX)	61354			C₁₃H₂₃N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

Acylation of 4-amino-1-benzylpiperidine (XVI) with 5-chlorovaleryl chloride (XVII) yielded chloro amide (XVIII). This was cyclized to the piperidino piperidinone (XIX) by treatment with NaH in THF. Subsequent hydrogenolysis of the N-benzyl group of (XIX) furnished piperidine (XX). Finally, reductive alkylation of piperidine (XX) with aldehyde (XV) in the presence of sodium triacetoxyborohydride gave rise to the title compound.

参考文献中间体

合成目标

【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .
【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	44276	3,5-dichloro-N-[(3R)-3-(3,4-dichlorophenyl)-2-(methoxyimino)-5-oxopentyl]-N-methylbenzamide		C₂₀H₁₈Cl₄N₂O₃	详情	详情
(XVI)	34808	1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine	50541-93-0	C₁₂H₁₈N₂	详情	详情
(XVII)	44277	5-chloropentanoyl chloride	1575-61-7	C₅H₈Cl₂O	详情	详情
(XVIII)	44278	N-(1-benzyl-4-piperidinyl)-5-chloropentanamide		C₁₇H₂₅ClN₂O	详情	详情
(XIX)	44279			C₁₇H₂₄N₂O	详情	详情
(XX)	44280	N-(4-Piperidine)-2-piperidinone		C₁₀H₁₈N₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Acylation of 4-amino-1-benzylpiperidine (I) with 5-chlorovaleryl chloride (II) affords amide (III). Intramolecular cyclization of the chlorovaleramide (III) in the presence of NaH leads to the bipiperidine compound (IV). The N-benzyl group of (IV) is then removed by catalytic hydrogenolysis to provide intermediate (V)

参考文献中间体

合成目标

【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .
【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 .

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)	34809	N-benzoyl-N'-(1-benzyl-4-piperidinyl)urea		C₂₀H₂₃N₃O₂	详情	详情
(II)	44277	5-chloropentanoyl chloride	1575-61-7	C₅H₈Cl₂O	详情	详情
(III)	44278	N-(1-benzyl-4-piperidinyl)-5-chloropentanamide		C₁₇H₂₅ClN₂O	详情	详情
(IV)	44279			C₁₇H₂₄N₂O	详情	详情
(V)	44280	N-(4-Piperidine)-2-piperidinone		C₁₀H₁₈N₂O	详情	详情

Extended Information