(3,5-dimethylphenyl)(2-methylcyclopropyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】52519

【品名】(3,5-dimethylphenyl)(2-methylcyclopropyl)methanone

【CA登记号】

【分子式】C₁₃H₁₆O

【分子量】188.26944

【元素组成】C 82.94% H 8.57% O 8.5%

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 intermediate ketone (VI) was prepared as follows: 2-Methylcyclopropanecarboxylic acid (I) was converted to the Weinreb amide (III) via activation as the corresponding acid chloride (II) followed by reaction with N,O-dimethylhydroxylamine. The organolithium reagent (V), prepared by metalation of 5-bromo-m-xylene (IV) with n-BuLi, was then added to the methoxy amide (III), producing the target aryl cyclopropyl ketone (VI).

参考文献中间体

合成目标

【1】 Chu, L.; Wyvratt, M.J.; Ponpipom, M.M.; Lin, P.; Ashton, W.T.; Goulet, M.; Young, J.; Girotra, N.N.; Fisher, M.H. (Merck & Co., Inc.); Antagonists of gonadotropin releasing hormone. EP 1095038; WO 0004013 .

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)	52514	2-Methylcyclopropanecarboxylic acid	29555-02-0	C₅H₈O₂	详情	详情
(II)	52515	2-methylcyclopropanecarbonyl chloride		C₅H₇ClO	详情	详情
(III)	52516	N,2-dimethyl-N-(methyloxy)cyclopropanecarboxamide		C₇H₁₃NO₂	详情	详情
(IV)	52517	5-Bromo-1,3-dimethylbenzene; 5-Bromo-m-xylene; 1-Bromo-3,5-dimethylbenzene; 3,5-Dimethylbromobenzene	556-96-7	C₈H₉Br	详情	详情
(V)	52518	(3,5-dimethylphenyl)lithium		C₈H₉Li	详情	详情
(VI)	52519	(3,5-dimethylphenyl)(2-methylcyclopropyl)methanone		C₁₃H₁₆O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Ethyl 2-(4-nitrophenyl)propionate (VIII), obtained by acid-catalyzed esterification of carboxylic acid (VII), was alkylated by means of iodomethane and NaH to furnish the 2-methylpropionate (IX). Subsequent nitro group hydrogenation over Pd/C gave aniline (X). Diazotization of (X), followed by SnCl2 reduction of the intermediate diazonium salt, afforded the aryl hydrazine (XI). Cyclization between hydrazine (XI) and ketone (VI) under Fischer indolization conditions occurred with concomitant cyclopropyl group rearrangement to generate the racemic beta-methyl tryptamine derivative (XII), which was further separated into the enantiomers.

参考文献中间体

合成目标

【1】 Chu, L.; Wyvratt, M.J.; Ponpipom, M.M.; Lin, P.; Ashton, W.T.; Goulet, M.; Young, J.; Girotra, N.N.; Fisher, M.H. (Merck & Co., Inc.); Antagonists of gonadotropin releasing hormone. EP 1095038; WO 0004013 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	52519	(3,5-dimethylphenyl)(2-methylcyclopropyl)methanone	C₁₃H₁₆O	详情	详情
(VII)	52520	2-(4-nitrophenyl)propanoic acid	C₉H₉NO₄	详情	详情
(VIII)	33983	ethyl 2-(4-nitrophenyl)propanoate	C₁₁H₁₃NO₄	详情	详情
(IX)	52521	ethyl 2-methyl-2-(4-nitrophenyl)propanoate	C₁₂H₁₅NO₄	详情	详情
(X)	52522	ethyl 2-(4-aminophenyl)-2-methylpropanoate	C₁₂H₁₇NO₂	详情	详情
(XI)	52523	ethyl 2-(4-hydrazinophenyl)-2-methylpropanoate	C₁₂H₁₈N₂O₂	详情	详情
(XII)	52524	ethyl 2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate	C₂₅H₃₂N₂O₂	详情	详情

Extended Information