4-piperidinylmethanol -Drug Synthesis Database

【结构式】

【分子编号】32954

【品名】4-piperidinylmethanol

【CA登记号】

【分子式】C₆H₁₃NO

【分子量】115.17536

【元素组成】C 62.57% H 11.38% N 12.16% O 13.89%

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：(II)

Reduction of ethyl 4-piperidinecarboxylate (I) with LiAlH4 in THF provided 4-piperidinemethanol (II), which was coupled with 3-ethoxybenzoyl chloride (III) in the presence of Et3N, yielding amide (IV). Subsequent treatment of (IV) with p-toluenesulfonyl chloride in pyridine afforded the corresponding tosylate (V. This was finally condensed with 5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline (VI) to furnish the title compound.

参考文献中间体

合成目标

【1】 George, P.; Sevrin, M.; Maloizel, C.; Tixidre, A.; Froissant, J. (Sanofi-Synthelabo ); Derivs. of 2-[(4-piperidinyl)methyl]-1,2,3, 4-tetrahydroisoquinoline, their use in therapy. AU 8929617; EP 0351255; JP 1990025481; US 4925850 .

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)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(II)	32954	4-piperidinylmethanol		C₆H₁₃NO	详情	详情
(III)	32955	3-ethoxybenzoyl chloride	61956-65-8	C₉H₉ClO₂	详情	详情
(IV)	32956	(3-ethoxyphenyl)[4-(hydroxymethyl)-1-piperidinyl]methanone		C₁₅H₂₁NO₃	详情	详情
(V)	32957	[1-(3-ethoxybenzoyl)-4-piperidinyl]methyl 4-methylbenzenesulfonate		C₂₂H₂₇NO₅S	详情	详情
(VI)	32958	5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 5-methoxy-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether		C₁₁H₁₅NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of 4-piperidinylmethanol (I) with 4-chloropyridine (II) gives 1-(4-pyridyl)piperidin-4-ylmethanol (III), which is oxidized with (COCl)2 and TEA in DMSO to yield the carbaldehyde (IV). The reductocondensation of (IV) with N-(tert-butoxycarbonyl)ethylene-1,2-diamine (V) by means of sodium triacetoxyborohydride and acetic acid affords the corresponding adduct as the borane complex (VI), which is acylated with bromoacetyl chloride (VII) and TEA in dichloromethane, providing the bromoacetamide (VIII). The cleavage of the boron complex and the Boc protecting group of (VIII) with TFA and anisole in ethyl ether gives the precursor (IX), which is cyclized to the piperazinone (X) by means of TEA in DMF. Finally, compound (X) is condensed with 6-chloronaphthalene-2-sulfonyl chloride by means of TEA in dichloromethane to yield the target sulfonamide.

参考文献中间体

合成目标

【1】 Nishida, H.; et al.; Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor. Chem Pharm Bull 2001, 49, 10, 1237.
【2】 Miyazaki, Y.; Mukaihira, T.; Nishida, H.; Hosaka, Y.; Matsusue, T. (Mochida Pharmaceutical Co., Ltd.); Aromatic cpds. having cyclic amino or salts thereof. EP 1048652; WO 9933805 .

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)	32954	4-piperidinylmethanol		C₆H₁₃NO	详情	详情
(II)	32889	4-chloropyridine	7379-35-3	C₅H₄ClN	详情	详情
(III)	45860	[1-(4-pyridinyl)-4-piperidinyl]methanol		C₁₁H₁₆N₂O	详情	详情
(IV)	52205	1-(4-pyridinyl)-4-piperidinecarbaldehyde		C₁₁H₁₄N₂O	详情	详情
(V)	13241	N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate	57260-73-8	C₇H₁₆N₂O₂	详情	详情
(VI)	52206			C₂₂H₃₇BN₄O₇	详情	详情
(VII)	27903	2-Bromoacetyl chloride	22118-09-8	C₂H₂BrClO	详情	详情
(VIII)	52207			C₂₄H₃₈BBrN₄O₈	详情	详情
(IX)	52208	N-(2-aminoethyl)-2-bromo-N-{[1-(4-pyridinyl)-4-piperidinyl]methyl}acetamide		C₁₅H₂₃BrN₄O	详情	详情
(X)	52209	1-{[1-(4-pyridinyl)-4-piperidinyl]methyl}-2-piperazinone		C₁₅H₂₂N₄O	详情	详情
(XI)	45865	6-chloro-2-naphthalenesulfonyl chloride		C₁₀H₆Cl₂O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVIII)

4-(Hydroxymethyl)piperidine (XVIII) is protected as the N-Boc derivative (XIX) with Boc2O in CH2Cl2. Conversion of alcohol (XIX) into the corresponding mesylate, followed by treatment with NaI in acetone, furnishes the alkyl iodide (XX). Quaternization of triphenylphosphine with iodide (XX) in refluxing acetonitrile gives rise to the phosphonium salt (XXI).

参考文献中间体

合成目标

【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Rosauer, K. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6265434; WO 0059503 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVIII)	32954	4-piperidinylmethanol	C₆H₁₃NO	详情	详情
(XIX)	40399	tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate	C₁₁H₂₁NO₃	详情	详情
(XX)	41239	tert-butyl 4-(iodomethyl)-1-piperidinecarboxylate	C₁₁H₂₀INO₂	详情	详情
(XXI)	65138	{[1-(tert-butoxycarbonyl)-4-piperidinyl]methyl}(triphenyl)phosphonium iodide	C₂₉H₃₅INO₂P	详情	详情

Extended Information