4-chloro-1-[(5-methyl-3-pyridinyl)methyl]piperidine -Drug Synthesis Database

【结构式】

【分子编号】16505

【品名】4-chloro-1-[(5-methyl-3-pyridinyl)methyl]piperidine

【CA登记号】

【分子式】C₁₂H₁₇ClN₂

【分子量】224.73316

【元素组成】C 64.13% H 7.62% Cl 15.78% N 12.47%

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：(VI)

The reaction of 2-cyano-3-methylpyridine (I) with H2SO4 in t-BuOH gives the N-tert-butylamide (II), which is treated with two equivalents of BuLi and the corresponding dianion alkylated with 3-chlorobenzyl chloride to afford amide (III). The treatment of (III) with POCl3 gives nitrile (IV), which is cyclized to ketone (V) by subsequent treatment with CF3SO3H and aqueous HCl. Reaction of ketone (V) with the Grignard derivative prepared from chloride (VI) affords alcohol (VII), which is finally dehydrated by H2SO4 to give UR-12592, as shown in Scheme 20491401a.

参考文献中间体

合成目标

【1】 Carceller, E.; Jiménez, P.J.; Salas, J. (J. Uriach & Cia., SA); Process for the preparation of 8-chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine. ES 9602107 .
【2】 García-Rafanell, J.; Rupatadine Fumarate. Drugs Fut 1996, 21, 10, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	20642	1-chloro-3-(chloromethyl)benzene; 3-Chlorobenzyl chloride	620-20-2	C₇H₆Cl₂	详情	详情
(I)	16500	3-methyl-2-pyridinecarbonitrile	20970-75-6	C₇H₆N₂	详情	详情
(II)	16501	N-(tert-butyl)-3-methyl-2-pyridinecarboxamide		C₁₁H₁₆N₂O	详情	详情
(III)	20643	N-(tert-butyl)-3-(3-chlorophenethyl)-2-pyridinecarboxamide		C₁₈H₂₁ClN₂O	详情	详情
(IV)	20644	3-(3-chlorophenethyl)-2-pyridinecarbonitrile		C₁₄H₁₁ClN₂	详情	详情
(V)	16504	8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one; 8-Chloro-10,11-dihydro-4-aza-5H-dibenzo[a,d]cycloheptan-5-one	31251-41-9	C₁₄H₁₀ClNO	详情	详情
(VI)	16505	4-chloro-1-[(5-methyl-3-pyridinyl)methyl]piperidine		C₁₂H₁₇ClN₂	详情	详情
(VII)	16506	8-chloro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinyl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol		C₂₆H₂₈ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The key intermediate (VI) is synthesized through the condensation of 5-methylnicotinic acid (VIII) with 4-hydroxypiperidine by means of DCC in DMF to give amide (IX), followed by reduction with POCl3 and NaBH4 to give the amino alcohol (X), which is treated with SOCl2.

参考文献中间体

合成目标

【1】 Carceller, E.; Jiménez, P.J.; Salas, J. (J. Uriach & Cia., SA); Process for the preparation of 8-chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine. ES 9602107 .
【2】 García-Rafanell, J.; Rupatadine Fumarate. Drugs Fut 1996, 21, 10, 1032.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(VI)	16505	4-chloro-1-[(5-methyl-3-pyridinyl)methyl]piperidine		C₁₂H₁₇ClN₂	详情	详情
(VIII)	16507	5-methylnicotinic acid	3222-49-9	C₇H₇NO₂	详情	详情
(IX)	16508	(4-hydroxypiperidino)(5-methyl-3-pyridinyl)methanone		C₁₂H₁₆N₂O₂	详情	详情
(X)	16509	1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinol		C₁₂H₁₈N₂O	详情	详情

Extended Information