1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine -Drug Synthesis Database

【结构式】

【分子编号】31463

【品名】1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine

【CA登记号】

【分子式】C₁₁H₂₂N₂

【分子量】182.30916

【元素组成】C 72.47% H 12.16% N 15.37%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(IV)

The alkylation of 4-piperidone monohydrate hydrochloride (I) with 5-bromo-2-methyl-2-pentene (II) in the presence of KI and K2CO3 afforded the tertiary amine (III). Subsequent reductive amination using ammonium acetate and sodium cyanoborohydride provided aminopiperidine (IV).

参考文献中间体

合成目标

【1】 Mase, T.; Mitsuya, M.; Tsuchiya, Y.; et al.; J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors. Bioorg Med Chem 1999, 7, 11, 2555.

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)	27115	4-piperidinone	40064-34-4	C₅H₉NO	详情	详情
(II)	31462	5-bromo-2-methyl-2-pentene		C₆H₁₁Br	详情	详情
(III)	31464	1-(4-methyl-3-pentenyl)-4-piperidinone		C₁₁H₁₉NO	详情	详情
(IV)	31463	1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine		C₁₁H₂₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Racemic 2-cyclopentyl-2-hydroxy-2-phenylacetic acid (V) was resolved by recrystallization of its cinchonidine salt from toluene to furnish the (-)-(R)-enantiomer (VI). Coupling with amine (IV) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and 1-hydroxybenzotriazole (HOBt) then gave the target amide.

参考文献中间体

合成目标

【1】 Mase, T.; Mitsuya, M.; Tsuchiya, Y.; et al.; J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors. Bioorg Med Chem 1999, 7, 11, 2555.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	31463	1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine		C₁₁H₂₂N₂	详情	详情
(V)	31465	2-cyclopentyl-2-hydroxy-2-phenylacetic acid; alpha-Cyclopentylmandelic acid	427-49-6	C₁₃H₁₆O₃	详情	详情
(VI)	31466	(2R)-2-cyclopentyl-2-hydroxy-2-phenylethanoic acid		C₁₃H₁₆O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The condensation of chiral dioxolane (I) with 2-cyclopentenone (II) by means of lithium diisopropylamide (LDA) in THF, followed by reaction with N-phenyl-trifluoromethanesulfonylimide gives the enol triflate (III), which is reduced with H2 over Pd/C in methanol yielding the chiral dioxolane (IV)(as major isomer (93:7)). The hydrolysis of (IV) with NaOH in methanol affords impure acid (V), which was purified through crystallization of its (-)-cinchonidine salt. Pure (V) is finally condensed with piperidine-4-amine (VI) by means of CDI and DIEA in DMF to afford the target amide.

参考文献中间体

合成目标

【1】 Mitsuya, M.; et al.; Stereoselective synthesis of a new muscarinic M3 receptor antagonist, J-104129. Bioorg Med Chem Lett 1999, 9, 14, 2037.

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)	31681	(2R,5R)-2-(tert-butyl)-5-phenyl-1,3-dioxolan-4-one		C₁₃H₁₆O₃	详情	详情
(II)	25950	2-cyclopenten-1-one	930-30-3	C₅H₆O	详情	详情
(III)	31682	(3S)-3-[(2R,4R)-2-(tert-butyl)-5-oxo-4-phenyl-1,3-dioxolan-4-yl]-1-cyclopenten-1-yl trifluoromethanesulfonate		C₁₉H₂₁F₃O₆S	详情	详情
(IV)	31683	(2R,5R)-2-(tert-butyl)-5-cyclopentyl-5-phenyl-1,3-dioxolan-4-one		C₁₈H₂₄O₃	详情	详情
(V)	31466	(2R)-2-cyclopentyl-2-hydroxy-2-phenylethanoic acid		C₁₃H₁₆O₃	详情	详情
(VI)	31463	1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine		C₁₁H₂₂N₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XII)

The alkylation of 4-(tert-butoxycarbonylamino)piperidine (VIII) with 5-bromo-2-methyl-2-pentene (IX) provided the tertiary amine (X). Cleavage of the Boc protecting group of (X) gave aminopiperidine (XI), which was finally coupled with the chiral hydroxyacid (IV) by means of carbonyl diimidazole.

参考文献中间体

合成目标

【1】 Tsuchiya, Y.; Nomoto, T.; Ohsawa, H.; Kawakami, K.; Ohwaki, K.; Nishikibe, M. (Banyu Pharmaceutical Co., Ltd.); 1,4-Disubstd. piperidine derivs.. EP 0823423; US 5750540; WO 9633973 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	31466	(2R)-2-cyclopentyl-2-hydroxy-2-phenylethanoic acid		C₁₃H₁₆O₃	详情	详情
(VIII)	41601	tert-butyl 4-piperidinylcarbamate; 4-tert-Boc-aminopiperidine	73874-95-0	C₁₀H₂₀N₂O₂	详情	详情
(IX)	31462	5-bromo-2-methyl-2-pentene		C₆H₁₁Br	详情	详情
(X)	41607	tert-butyl 1-(4-methyl-3-pentenyl)-4-piperidinylcarbamate		C₁₆H₃₀N₂O₂	详情	详情
(XII)	31463	1-(4-methyl-3-pentenyl)-4-piperidinamine; 1-(4-methyl-3-pentenyl)-4-piperidinylamine		C₁₁H₂₂N₂	详情	详情

Extended Information