N-(4-Piperidine)-2-piperidinone -Drug Synthesis Database

【结构式】

【分子编号】44280

【品名】N-(4-Piperidine)-2-piperidinone

【CA登记号】

【分子式】C₁₀H₁₈N₂O

【分子量】182.2658

【元素组成】C 65.9% H 9.95% N 15.37% O 8.78%

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：(XX)

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2

该中间体在本合成路线中的序号：(V)

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

合成路线3

该中间体在本合成路线中的序号：(V)

Reductive condensation between aldehyde (XIV) and the piperidine derivative (V) in the presence of NaBH3CN leads to the N-alkylated piperidine (XV). The N-Boc group of (XV) is cleaved under acidic conditions to afford amine (XVI), which is further acylated by 3,5-dichlorobenzoyl chloride (XVII), providing benzamide (XVIII). The oxime O-allyl group of (XVIII) is then removed by treatment with palladium tetrakis(triphenylphosphine) and triethylammonium formate, yielding oxime (XIX). This is subsequently alkylated with bromoacetonitrile and NaH, affording (XX)

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
(V)	44280	N-(4-Piperidine)-2-piperidinone		C₁₀H₁₈N₂O	详情	详情
(XIV)	60820	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate		C₂₀H₂₆Cl₂N₂O₄	详情	详情
(XV)	60821			C₃₀H₄₄Cl₂N₄O₄	详情	详情
(XVI)	60822			C₂₅H₃₆Cl₂N₄O₂	详情	详情
(XVII)	27769	3,5-dichlorobenzoyl chloride	2905-62-6	C₇H₃Cl₃O	详情	详情
(XVIII)	60823			C₃₂H₃₈Cl₄N₄O₃	详情	详情
(XIX)	60824			C₂₉H₃₄Cl₄N₄O₃	详情	详情
(XX)	60825			C₃₁H₃₅Cl₄N₅O₃	详情	详情

Extended Information