Indole-2-carboxylic acid ethyl ester; 2-Carbethoxyindole; 1H-indole-2-carboxylic acid ethyl ester -Drug Synthesis Database

【结构式】

【分子编号】27783

【品名】Indole-2-carboxylic acid ethyl ester; 2-Carbethoxyindole; 1H-indole-2-carboxylic acid ethyl ester

【CA登记号】3770-50-1

【分子式】C₁₁H₁₁NO₂

【分子量】189.21388

【元素组成】C 69.83% H 5.86% N 7.4% O 16.91%

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)

[U-14C]-Aniline (I) is converted to [U-14C]phenyldiazonium chloride (II), which is condensed in situ with ethyl 2-(ethoxyalyl)propionate (III) to give [U-14C]phenylhydrazone of ethyl pyruvate (IV). Cyclization of (IV) by polyphosphoric acid in xylene affords ethyl [U-14C-phenyl]indole-2-carboxylic acid (V). Catalytic hydrogenation of compound (V) in the presence of platinum gives ethyl [U-14C-cyclohexyl]-(RS)-perhydroindole-2-carboxylic acid (VI), which is saponified to the corresponding acid (VIII). Compound (VI) can also be prepared by reduction of compound (V) with tin and hydrochloric acid to give compound (VII), and hydrogenation of the latter in the presence of palladium. Compound (VIII) is reesterified to the benzyl ester (IX), which is condensed with N-[(S)-1-carbethoxybutyl]-(S)-alanine (X) in the presence of DCC and 1-hydroxy-1-benzotriazole. The resulting compound (X) is separated fom the mixture of isomers by silica gel column chromatography. Hydrogenolysis of the latter compound gives [U-14C-cyclohexyl]perindopril, which is isolated as the tert-bytylamine salt.

参考文献中间体

合成目标

【1】 Pichat, L.; et al.; Syntheses du S-9490-3. J Label Compd Radiopharm 1988, 25, 5, 553.

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)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(II)	25897	benzenediazonium chloride		C₆H₅ClN₂	详情	详情
(III)	27781	diethyl 2-methyl-3-oxosuccinate	5965-53-7	C₉H₁₄O₅	详情	详情
(IV)	27782	ethyl 2-[(E)-2-phenylhydrazono]propanoate		C₁₁H₁₄N₂O₂	详情	详情
(V)	27783	Indole-2-carboxylic acid ethyl ester; 2-Carbethoxyindole; 1H-indole-2-carboxylic acid ethyl ester	3770-50-1	C₁₁H₁₁NO₂	详情	详情
(VI)	27784	ethyl octahydro-1H-indole-2-carboxylate		C₁₁H₁₉NO₂	详情	详情
(VII)	27785	ethyl 2-indolinecarboxylate		C₁₁H₁₃NO₂	详情	详情
(VIII)	27789	octahydro-1H-indole-2-carboxylic acid		C₉H₁₅NO₂	详情	详情
(IX)	27790	benzyl octahydro-1H-indole-2-carboxylate		C₁₆H₂₁NO₂	详情	详情
(X)	27786	(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]propionic acid		C₁₀H₁₉NO₄	详情	详情
(XI)	27787	benzyl (2S,3aS,7aS)-1-((2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]propanoyl)octahydro-1H-indole-2-carboxylate		C₂₆H₃₈N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of ethyl indole-2-carboxylate (I) with dodecanoic acid (II) in the presence of polyphosphoric acid and trifluoroacetic anhydride produced the corresponding 3-dodecanoylindole (III). Subsequent alkylation of (III) with ethyl 4-(2-bromoethoxy)phenylacetate (IV) using potassium tert-butoxide in DMSO afforded the N-alkylated indole (V). The ethyl ester groups of (V) were finally hydrolyzed with KOH to provide the target diacid compound.

参考文献中间体

合成目标

【1】 Lehr, M. (Merckle GmbH); Acylpyrroldicarboxylic acids and acylindoldicarboxylic acids and their derivs. and inhibitors of the cytosolic phospholipase A2. EP 0923546; WO 9805637 .

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)	27783	Indole-2-carboxylic acid ethyl ester; 2-Carbethoxyindole; 1H-indole-2-carboxylic acid ethyl ester	3770-50-1	C₁₁H₁₁NO₂	详情	详情
(II)	30803	lauric acid	143-07-7	C₁₂H₂₄O₂	详情	详情
(III)	30804	ethyl 3-dodecanoyl-1H-indole-2-carboxylate		C₂₃H₃₃NO₃	详情	详情
(IV)	30805	ethyl 2-[4-(2-bromoethoxy)phenyl]acetate		C₁₂H₁₅BrO₃	详情	详情
(V)	30806	ethyl 3-dodecanoyl-1-[2-[4-(2-ethoxy-2-oxoethyl)phenoxy]ethyl]-1H-indole-2-carboxylate		C₃₅H₄₇NO₆	详情	详情

Extended Information