octanenitrile -Drug Synthesis Database

【结构式】

【分子编号】59081

【品名】octanenitrile

【CA登记号】124-12-9

【分子式】C₈H₁₅N

【分子量】125.21384

【元素组成】C 76.74% H 12.07% N 11.19%

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：(XII)

Reformatskii condensation of the organozinc reagent derived from methyl bromoacetate (XIII) with n-heptyl cyanide (XII) gave rise to the keto ester adduct (XIV). Catalytic hydrogenation of (XIV) in the presence of the chiral catalyst generated from dichloro(cycloocta-1,5-diene)ruthenium and (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl furnished the (R)-hydroxyester (XV) in high enantiomeric excess. Ester group reduction in (XV) by means of LiAlH4 afforded diol (XVI), which was further converted to the primary tosylate (XVII) with p-toluenesulfonyl chloride in pyridine. Then, alkylation of the intermediate alcohol (XI) with tosylate (XVII) under Williamson's ether synthesis conditions provided the common precursor (XVIII).

参考文献中间体

合成目标

【1】 Christ, W.J.; Kawata, T.; Hawkins, L.D.; Kobayashi, S.; Asano, O.; Rossignol, D.P. (Eisai Co., Ltd.); Anti-endotoxin cpds.. EP 0536969; JP 1993194470; US 5530113 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	59080	(4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol		C₁₅H₂₉N₃O₅Si	详情	详情
(XII)	59081	octanenitrile	124-12-9	C₈H₁₅N	详情	详情
(XIII)	12309	methyl 2-bromoacetate; methyl bromoacetate	96-32-2	C₃H₅BrO₂	详情	详情
(XIV)	59082	methyl 3-oxodecanoate		C₁₁H₂₀O₃	详情	详情
(XV)	59083	methyl (3R)-3-hydroxydecanoate		C₁₁H₂₂O₃	详情	详情
(XVI)	59084	(3R)-1,3-decanediol		C₁₀H₂₂O₂	详情	详情
(XVII)	49121	(3R)-3-hydroxydecyl 4-methylbenzenesulfonate		C₁₇H₂₈O₄S	详情	详情
(XVIII)	59085	(3R)-1-[((4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy]-3-decanol		C₂₅H₄₉N₃O₆Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXVII)

Intermediates (III) and (XII) are prepared as follows:
Trimethyl orthooctanoate (XII) is prepared by Pinner reaction of octanonitrile (XXXVII) with MeOH in the presence of HCl in MeOAc followed by treatment of the resulting methyl octanimidate hydrochloride (XXXVIII) with MeOH in methylcyclohexane (3). Scheme 5.
Intermediate (III) can be prepared by consecutive N-protection of the amidine nitrogens in pyrazole-1-carboxamidine (XIV), first by treatment with Boc2O by means of DIEA in DMF, and then reaction of the resulting monoprotected intermediate (XXXIX) with Boc2O in the presence of NaH in THF (3). Scheme 5.

参考文献中间体

合成目标

【3】 Nakamura, Y., Murakami, M., Yamaoka, M., Wakayama, M., Umeo, K. (Daiichi Sankyo Co., Ltd.). Method for manufacturing neuraminic acid derivatives. EP 2132191, JP 2010523472, WO 2008126943.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	52079	sodium (Z)-1-cyano-3-ethoxy-3-oxo-1-propen-2-olate	627076-29-3	C₆H₆NNaO₃	详情	详情
(XII)	66000	trimethyl orthooctanoate; 1,1,1-Trimethoxyoctane	161838-87-5	C₁₁H₂₄O₃	详情	详情
(XIV)	15983	1H-pyrazole-1-carboximidamide	4023-00-1	C₄H₆N₄	详情	详情
(XXXVII)	59081	octanenitrile	124-12-9	C₈H₁₅N	详情	详情
(XXXVIII)	66024			C₉H₁₉NO.HCl	详情	详情
(XXXIX)	66025	N-(tert-Butoxycarbonyl)-1H-pyrazole-1-carboxamidine; N-Boc-1H-pyrazole-1-carboxamidine	152120-61-1	C₉H₁₄N₄O₂	详情	详情

Extended Information