1-cyclooctene-1-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】37975

【品名】1-cyclooctene-1-carbaldehyde

【CA登记号】

【分子式】C₉H₁₄O

【分子量】138.20956

【元素组成】C 78.21% H 10.21% O 11.58%

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：(V)

Coupling between 2,7-dichloroxanthene-9-carboxylic acid (I) and 4-amino-1-tert-butoxycarbonylpiperidine (II) in the presence of EDC and HOBt afforded amide (III). After acidic cleavage of the Boc protecting group of (III), the resulting amine (IV) was reductively condensed with 1-cyclooctene carbaldehyde (V) by means of NaBH(OAc)3 to yield the cyclooctenylmethyl amine (VI). Subsequent alkylation of the tertiary amine (VI) with iodoethane gave rise to the target ammonium salt. Separation of the geometric isomers was carried out by column chromatography.

参考文献中间体

合成目标

【1】 Naya, A.; et al.; Design, synthesis, and discovery of a novel CCR1 antagonist. J Med Chem 2001, 44, 9, 1429.
【2】 Naya, A.; Owada, Y.; Saeki, T.; Ohwaki, K.; Iwasawa, Y. (Banyu Pharmaceutical Co., Ltd.); Chemokine receptor antagonists. EP 0916668; WO 9804554 .

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)	37972	2,7-dichloro-9H-xanthene-9-carboxylic acid		C₁₄H₈Cl₂O₃	详情	详情
(II)	28414	4-Amino-1-N-Boc-piperidine; tert-butyl 4-amino-1-piperidinecarboxylate; N-Boc-4-aminopiperidine	87120-72-7	C₁₀H₂₀N₂O₂	详情	详情
(III)	37973	tert-butyl 4-[[(2,7-dichloro-9H-xanthen-9-yl)carbonyl]amino]-1-piperidinecarboxylate		C₂₄H₂₆Cl₂N₂O₄	详情	详情
(IV)	37974	2,7-dichloro-N-(4-piperidinyl)-9H-xanthene-9-carboxamide		C₁₉H₁₈Cl₂N₂O₂	详情	详情
(V)	37975	1-cyclooctene-1-carbaldehyde		C₉H₁₄O	详情	详情
(VI)	37976	2,7-dichloro-N-[1-(1-cycloocten-1-ylmethyl)-4-piperidinyl]-9H-xanthene-9-carboxamide		C₂₈H₃₂Cl₂N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Cyclooctanone tosylhydrazone was treated with n-BuLi and subsequently reacted with DMF to afford (II). Compound (III) was prepared from 4-tert-butoxycarbonylpiperidine by reductive alkylation with (II). Deprotection of (III) and condensation with 2,7-dichloroxanthen-9-carboxylic acid (IV) using 1,1'-carbonyldiimidazole (CDI) afforded (V). Compound (V) was quaternarized with iodoethane to provide a quaternary ammonium derivative as a mixture of two isomers (cis and trans) attributed to the 4-substituted piperidinium structure in a ratio of 2:1. Finally, the mixture was separated by silica gel column chromatography to give a major isomer, J-113863.

参考文献中间体

合成目标

【1】 Naya, A.; et al.; Design, synthesis, and discovery of a novel CCR1 antagonist. J Med Chem 2001, 44, 9, 1429.
【2】 Saeki, T.; Naya, A.; J-113863. Drugs Fut 2001, 26, 2, 121.

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)	14209	Cyclooctanone	502-49-8	C₈H₁₄O	详情	详情
(II)	37975	1-cyclooctene-1-carbaldehyde		C₉H₁₄O	详情	详情
(III)	41601	tert-butyl 4-piperidinylcarbamate; 4-tert-Boc-aminopiperidine	73874-95-0	C₁₀H₂₀N₂O₂	详情	详情
(IV)	44356	tert-butyl 1-(1-cycloocten-1-ylmethyl)-4-piperidinylcarbamate		C₁₉H₃₄N₂O₂	详情	详情
(V)	37972	2,7-dichloro-9H-xanthene-9-carboxylic acid		C₁₄H₈Cl₂O₃	详情	详情
(VI)	37976	2,7-dichloro-N-[1-(1-cycloocten-1-ylmethyl)-4-piperidinyl]-9H-xanthene-9-carboxamide		C₂₈H₃₂Cl₂N₂O₂	详情	详情

Extended Information