ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】34308

【品名】ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate

【CA登记号】

【分子式】C₁₁H₁₃NO₂

【分子量】191.22976

【元素组成】C 69.09% H 6.85% N 7.32% O 16.73%

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：(II)

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：(I)

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：(I)

Indoline-2-carboxylic acid (I) is converted into the N-Boc derivative (II) by treatment with Boc2O. Subsequent coupling of (II) with methyl indoline-2-carboxylate (III) by using 2-chloro-1-methylpyridinium iodide (CMPI) provides amide (IV). Hydrolysis of the methyl ester function of (IV) employing LiOH leads to carboxylic acid (V). This is then coupled to N-epsilon-(benzyloxycarbonyl)-lysine methyl ester (VI) in the presence of CMPI to furnish the title compound.

参考文献中间体

合成目标

【1】 Reichert, D.; Kutscher, B.; Bang, H.; Brune, K.; Quinkert, G.; Schaible, H.-G. (Asta Medica AG); Specific immunophilin ligands as antiasthmatics and immunosuppressants. DE 19616509; EP 0896580; JP 2000500776; WO 9741148 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	34308	ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate	C₁₁H₁₃NO₂	详情	详情
(II)	61011	1-(tert-butoxycarbonyl)-2-indolinecarboxylic acid	C₁₄H₁₇NO₄	详情	详情
(III)	61012	methyl 2-indolinecarboxylate	C₁₀H₁₁NO₂	详情	详情
(IV)	61013	tert-butyl 2-{[2-(methoxycarbonyl)-2,3-dihydro-1H-indol-1-yl]carbonyl}-1-indolinecarboxylate	C₂₄H₂₆N₂O₅	详情	详情
(V)	61014	1-{[1-(tert-butoxycarbonyl)-2,3-dihydro-1H-indol-2-yl]carbonyl}-2-indolinecarboxylic acid	C₂₃H₂₄N₂O₅	详情	详情
(VI)	31069	methyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate	C₁₅H₂₂N₂O₄	详情	详情

Extended Information