(2S)-2,3-dihydro-1H-indole-2-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】34307

【品名】(2S)-2,3-dihydro-1H-indole-2-carboxylic acid

【CA登记号】

【分子式】C₉H₉NO₂

【分子量】163.176

【元素组成】C 66.25% H 5.56% N 8.58% O 19.61%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

The esterification of indoline-2-carboxylic acid (I) with ethanol HCl gives the corresponding ethyl ester (II), which is acylated with 3-(benzoylthio)-2-methylpropionyl chloride (III) by means of K2CO3 in methylene chloride yielding ethyl N-[3-(benzoylthio)-2-methylpropionyl]indoline-2-carboxylate (IV). The deprotection of (IV) with hydrazine in the same solvent affords ethyl N-(3-mercapto-2-methylpropionyl)indoline-2-carboxylate (V), which is finally saponified with KOH in methanol water.

参考文献中间体

合成目标

【1】 Stanton, J.L.; et al.; Angiotensin converting enzyme inhibitors: N-Substituted monocyclic and bibyvlic amino acid deivatives. J Med Chem 1983, 26, 9, 1267-77.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	34307	(2S)-2,3-dihydro-1H-indole-2-carboxylic acid	C₉H₉NO₂	详情	详情
(II)	34308	ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate	C₁₁H₁₃NO₂	详情	详情
(III)	34309	S-[(2S)-3-chloro-2-methyl-3-oxopropyl] benzenecarbothioate	C₁₁H₁₁ClO₂S	详情	详情
(IV)	34310	ethyl (2S)-1-[(2R)-3-(benzoylsulfanyl)-2-methylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylate	C₂₂H₂₃NO₄S	详情	详情
(V)	34311	ethyl (2S)-1-[(2R)-2-methyl-3-sulfanylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylate	C₁₅H₁₉NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

This compound can be obtained by several related ways: 1) The hydrolysis of ethyl indoline 2 carboxylate (I) with KOH in aqueous DMSO gives indoline 2-carboxylic acid (II), which is acylated with 3-(benzoylthio)-2-methylpropanoyl chloride (III) in methylene chloride yielding 1-[3-(benzoylthio)-2-methyl-1-oxopropyl]indoline-2-carboxylic acid (IV). Finally, this compound is debenzoylated by treatment with 2-methoxyethylamine (A). 2) The acylation of (I) with methacryloyl chloride (V) by means of triethylamine in ether yields ethyl 1-methacryloylindoline-2-carboxylate (VI), which is hydrolyzed with KOH in aqueous DMSO affording 1-methacryloylindoline-2-carboxylic acid (VII). Finally, this compound is treated with thiobenzoic acid (VIII) and 4-dimethylaminopyridine in acetone to give (IV), previously synthesized. 3) The acylation of acid (II) with (V) as before also gives (VII).

参考文献中间体

合成目标

【1】 Kim, D.H.; et al.; Mercaptopropanoyl)indoline-2-carboxylic acids and related compounds as potent angiotensin converting enzyme inhibitors and antihypertensive agents. J Med Chem 1983, 26, 3, 394-403.
【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; WY-44221. Drugs Fut 1983, 8, 11, 953.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	34675	2-methoxyethylamine; 2-methoxy-1-ethanamine	109-85-3	C₃H₉NO	详情	详情
(I)	34308	ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate		C₁₁H₁₃NO₂	详情	详情
(II)	34307	(2S)-2,3-dihydro-1H-indole-2-carboxylic acid		C₉H₉NO₂	详情	详情
(III)	34309	S-[(2S)-3-chloro-2-methyl-3-oxopropyl] benzenecarbothioate		C₁₁H₁₁ClO₂S	详情	详情
(IV)	36214	(2S)-1-[(2R)-3-(benzoylsulfanyl)-2-methylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylic acid		C₂₀H₁₉NO₄S	详情	详情
(V)	33553	2-methylacryloyl chloride	920-46-7	C₄H₅ClO	详情	详情
(VI)	36211	ethyl (2S)-1-methacryloyl-2,3-dihydro-1H-indole-2-carboxylate		C₁₅H₁₇NO₃	详情	详情
(VII)	36212	(2S)-1-methacryloyl-2,3-dihydro-1H-indole-2-carboxylic acid		C₁₃H₁₃NO₃	详情	详情
(VIII)	36213	benzenecarbothioic S-acid	98-91-9	C₇H₆OS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The ethanolysis of 2,4-dimethylglutaric anhydride (I) gives the monoethyl ester of 2,4-dimethylglutaric acid (II), which by reaction with oxalyl chloride is converted into the monoacyl chloride (III). Finally, this compound is condensed with indoline-2-carboxylic acid (IV) hy means of K2CO3 in pyridine.

参考文献中间体

合成目标

【1】 Gruenfeld, N (Novartis AG); 1-Carboxyalkanoylindolin-2-carboxylic acids and derivs. thereof, processes for their preparation, and pharmaceutical compsns. containing these cpds. as well as their use. EP 0050850 .
【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; CGS-13945. Drugs Fut 1983, 8, 12, 1010.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	36176	3,5-dimethyldihydro-2H-pyran-2,6(3H)-dione	C₇H₁₀O₃	详情	详情
(II)	36177	(2R,4R)-5-ethoxy-2,4-dimethyl-5-oxopentanoic acid	C₉H₁₆O₄	详情	详情
(III)	36178	ethyl (2R,4R)-5-chloro-2,4-dimethyl-5-oxopentanoate	C₉H₁₅ClO₃	详情	详情
(IV)	34307	(2S)-2,3-dihydro-1H-indole-2-carboxylic acid	C₉H₉NO₂	详情	详情

Extended Information