1-(methoxycarbonyl)cyclopropanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】58459

【品名】1-(methoxycarbonyl)cyclopropanecarboxylic acid

【CA登记号】113020-21-6

【分子式】C₆H₈O₄

【分子量】144.12712

【元素组成】C 50% H 5.59% O 44.4%

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：(II)

Partial hydrolysis of dimethyl 1,1-cyclopropanedicarboxylate (I) yields mono-acid (II). Curtius rearrangement of (II), followed by treatment with methanol provides the methyl carbamate (III), which is N-methylated to (IV) employing iodomethane and NaH in DMF. Reduction of the carboxylate and carbamate groups of (IV) by means of LiAlH4 furnishes amino alcohol (V). After chlorination of (V) with SOCl2, the resultant alkyl chloride (VI) is displaced by NaCN to afford nitrile (VII). Hydrolysis of (VII) with methanolic HCl leads to ester (VIII), which is further reduced to amino alcohol (IX) using LiAlH4. Acylation of alcohol (IX) with dimethylcarbamoyl chloride produces the target amino carbamate, which is finally isolated as the corresponding fumarate salt.

参考文献中间体

合成目标

【1】 Guillonneau, C.; Lestage, P.; Charton, Y.; Lockhart, B.; Goldstein, S. (Servier Laboratoires); 1,1- And 1,2-disubstd. cyclopropanes, process for their preparation and pharmaceutical compsns. thereof. EP 1170281; FR 2810664; JP 2002069046; US 2002022643 .

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)	58458	dimethyl 1,1-cyclopropanedicarboxylate; cyclopropane-1,1-dicarboxylic acid dimethyl ester; 1,1-cyclopropanedicarboxylic acid dimethyl ester	6914-71-2	C₇H₁₀O₄	详情	详情
(II)	58459	1-(methoxycarbonyl)cyclopropanecarboxylic acid	113020-21-6	C₆H₈O₄	详情	详情
(III)	58460	methyl 1-[(methoxycarbonyl)amino]cyclopropanecarboxylate		C₇H₁₁NO₄	详情	详情
(IV)	58461	methyl 1-[(methoxycarbonyl)(methyl)amino]cyclopropanecarboxylate		C₈H₁₃NO₄	详情	详情
(V)	58462	[1-(dimethylamino)cyclopropyl]methanol		C₆H₁₃NO	详情	详情
(VI)	58463	1-(chloromethyl)-N,N-dimethylcyclopropanamine; N-[1-(chloromethyl)cyclopropyl]-N,N-dimethylamine		C₆H₁₂ClN	详情	详情
(VII)	58464	2-[1-(dimethylamino)cyclopropyl]acetonitrile		C₇H₁₂N₂	详情	详情
(VIII)	58465	methyl 2-[1-(dimethylamino)cyclopropyl]acetate		C₈H₁₅NO₂	详情	详情
(IX)	58466	2-[1-(dimethylamino)cyclopropyl]-1-ethanol		C₇H₁₅NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXIV)

Intermediate (XIV) is obtained by selective hydrolysis of dimethyl 1,1-cyclopropanedicarboxylate (XXIII) using NaOH in MeOH/H2O to afford acid-ester (XXIV), which by treatment with ClCO2Et in THF gives the mixed anhydride (XXV). Reduction of carboxylic anhydride (XXV) using NaBH4 in MeOH gives the primary alcohol (XXVI), which is finally activated as mesylate (XIV) by means of MsCl in the presence of DIEA in CH2Cl2 at 0 °C .

参考文献中间体

合成目标

【1】 Chen, G.P. (Advenchen Laboratories, LLC). Spiro substituted compounds as angiogenesis inhibitors. KR 2015039889; US 8163923; EP 2125777; JP 2010521474; WO 2008112408; US 2008227812.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	67637	1-(4-hydroxy-3-methoxyphenyl)ethanone		C₇H₁₂O₅S	详情	详情
(XXIII)	58458	dimethyl 1,1-cyclopropanedicarboxylate; cyclopropane-1,1-dicarboxylic acid dimethyl ester; 1,1-cyclopropanedicarboxylic acid dimethyl ester	6914-71-2	C₇H₁₀O₄	详情	详情
(XXIV)	58459	1-(methoxycarbonyl)cyclopropanecarboxylic acid	113020-21-6	C₆H₈O₄	详情	详情
(XXV)	67645	(ethyl carbonic) 1-(methoxycarbonyl)cyclopropanecarboxylic anhydride		C₉H₁₂O₆	详情	详情
(XXVI)	67646	methyl 1-(hydroxymethyl)cyclopropanecarboxylate		C₆H₁₀O₃	详情	详情

Extended Information