(2S)-2-amino-3-(1H-indol-3-yl)propanamide -Drug Synthesis Database

【结构式】

【分子编号】48206

【品名】(2S)-2-amino-3-(1H-indol-3-yl)propanamide

【CA登记号】

【分子式】C₁₁H₁₃N₃O

【分子量】203.24384

【元素组成】C 65.01% H 6.45% N 20.67% O 7.87%

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)

Coupling of Boc-Trp-OH (I) onto BHA resin by means of diisopropylcarbodiimide (DIPCDI) and HOBt in DMF followed by Boc removal by treatment with TFA in CH2Cl2 in the presence of mercaptoethanol provides on resin amino acid (II), which is converted into dipeptide (III) by coupling with Boc-Cys(Mbz)-OH by means of DIPCDI and HOBt followed by Boc removal by means of TFA in CH2Cl2. The same protocol of coupling and deprotection is followed for the incorporation of Boc-Val-OH and Boc-Lys(2-ClZ)-OH to furnish anchored tripeptide (IV), which is converted into protected octapeptide (V) by sequential amino acid couplings and deprotections by following the protocol described above. Simultaneous cleavage and protecting groups removal of resin (V) by treatment with HF in the presence of cresol and 1,2-ethanedithiol provides linear peptide (VI), which is finally oxidized by means of potassium ferrocyanide to furnish the desired product.

参考文献中间体

合成目标

【1】 Schally, A.V.; Cai, R.Z.; Biologically active octapeptides. US 4650787 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(G)	22184	(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid		C₁₄H₁₉NO₄	详情	详情
(E)	43774	6-chloro-5-(methylsulfanyl)-1H-indole; 6-chloro-1H-indol-5-yl methyl sulfide		C₉H₈ClNS	详情	详情
(A),(F)	48335	Boc-Cys(pMeOBzl)-OH; Boc-S-(4-methoxybenzyl)-L-cysteine; Boc-Cys(4MeOBzl)-OH; Boc-L-Cysteine(4-Methoxybenzyl); N-alpha-t-Boc-S-(p-methoxybenzyl)-L-cysteine; Boc-Cys(4-Mob)-OH; Boc-S-(4-methoxybenzyl) Cysteine; Boc-S-4-methoxybenzyl-L-cysteine	18942-46-6	C₁₆H₂₃NO₅S	详情	详情
(D)	48341	(2R)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid		C₁₆H₂₀N₂O₄	详情	详情
(I)	16114	N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid	13139-14-5	C₁₆H₂₀N₂O₄	详情	详情
(II)	48206	(2S)-2-amino-3-(1H-indol-3-yl)propanamide		C₁₁H₁₃N₃O	详情	详情
(III)	48337	(2R)-2-amino-N-[(1S)-2-amino-1-(1H-indol-3-ylmethyl)-2-oxoethyl]-3-[(4-methoxybenzyl)sulfanyl]propanamide		C₂₂H₂₆N₄O₃S	详情	详情
(IV)	48338	2-chlorobenzyl (5S)-5-amino-6-[((1S)-1-[[((1R)-2-[[(1S)-2-amino-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]-1-[[(4-methoxybenzyl)sulfanyl]methyl]-2-oxoethyl)amino]carbonyl]-2-methylpropyl)amino]-6-oxohexylcarbamate		C₄₁H₅₂ClN₇O₇S	详情	详情
(V)	48339	4-((2S,5R,8S,11S,14R,17S)-18-amino-2-([(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-[(4-methoxybenzyl)sulfanyl]propanoyl]amino)-8-[4-([[(2-chlorobenzyl)oxy]carbonyl]amino)butyl]-5,17-bis(1H-indol-3-ylmethyl)-11-isopropyl-14-[[(4-methoxybenzyl)sulfanyl]methyl]-3,6,9,12,15,18-hexaoxo-4,7,10,13,16-pentaazaoctadec-1-yl)phenyl 2-bromobenzyl carbonate		C₈₉H₉₈BrClN₁₂O₁₅S₂	详情	详情
(VI)	48340	(2S,5R,8S,11S,14R,17S,20R,23R)-23-amino-11-(4-aminobutyl)-17-(4-hydroxybenzyl)-2,14-bis(1H-indol-3-ylmethyl)-8-isopropyl-4,7,10,13,16,19,22-heptaoxo-24-phenyl-5,20-bis(sulfanylmethyl)-3,6,9,12,15,18,21-heptaazatetracosan-1-amide		C₅₇H₇₂N₁₂O₉S₂	详情	详情
(C)	31374	(2S)-2-[(tert-butoxycarbonyl)amino]-6-([[(2-chlorobenzyl)oxy]carbonyl]amino)hexanoic acid		C₁₉H₂₇ClN₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The title compound was prepared starting from the phosphinic dipeptide (I). Deprotection of the tert-butyl ester of (I) under acidic conditions afforded the carboxylic acid (II). This was then coupled with tryptophan amide (III) using EDC and HOBt to produce (IV). Finally, conjugate addition of 2-naphthalenethiol (V) to (IV) in the presence of NaOEt furnished the target thioether.

参考文献中间体

合成目标

【1】 Matziari, M.; Georgiadis, D.; Dive, V.; Yiotakis, A.; Convenient synthesis and diversification of dehydroalaninyl phosphinic peptide analogues. Org Lett 2001, 3, 5, 659.

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)	48204	(1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl[2-(tert-butoxycarbonyl)-2-propenyl]phosphinic acid		C₂₄H₃₀NO₆P	详情	详情
(II)	48205	2-[[((1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)(hydroxy)phosphoryl]methyl]acrylic acid		C₂₀H₂₂NO₆P	详情	详情
(III)	48206	(2S)-2-amino-3-(1H-indol-3-yl)propanamide		C₁₁H₁₃N₃O	详情	详情
(IV)	48207	2-([[(1S)-2-amino-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-2-propenyl((1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphinic acid		C₃₁H₃₃N₄O₆P	详情	详情
(V)	15234	2-Naphthalenethiol; 2-Naphthylhydrosulfide	91-60-1	C₁₀H₈S	详情	详情

Extended Information