6-chloro-5-(methylsulfanyl)-1H-indole; 6-chloro-1H-indol-5-yl methyl sulfide -Drug Synthesis Database

【结构式】

【分子编号】43774

【品名】6-chloro-5-(methylsulfanyl)-1H-indole; 6-chloro-1H-indol-5-yl methyl sulfide

【CA登记号】

【分子式】C₉H₈ClNS

【分子量】197.68796

【元素组成】C 54.68% H 4.08% Cl 17.93% N 7.09% S 16.22%

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：(E)

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 heating of nicotinoyl azide (I) in refluxing toluene gives the corresponding isocyanate (II), which without isolation is condensed with 6-chloro-5-(methylsulfanyl)indoline (IV) to afford the target compound. Intermediate indoline (IV) is obtained by reduction of 6-chloro-5-(methylsulfanyl)indole (III) with NaBH3CN in HOAc.

参考文献中间体

合成目标

【1】 Ham, P.; Jones, G.E.; Forbes, I.T. (SmithKline Beecham plc); Indoline derivs. as 5HT2C antagonists. EP 0707581; JP 1996512299; US 5834494; WO 9501976 .
【2】 Davies, D.T.; Bromidge, S.M.; Dabbs, S.; et al.; Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl)indolines that are potent and selective 5-HT2C/2B receptor antagonists. Bioorg Med Chem 1999, 7, 12, 2767.

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)	13619	Nicotinoyl azide		C₆H₄N₄O	详情	详情
(II)	27045	3-isocyanatopyridine	15268-31-2	C₆H₄N₂O	详情	详情
(III)	43774	6-chloro-5-(methylsulfanyl)-1H-indole; 6-chloro-1H-indol-5-yl methyl sulfide		C₉H₈ClNS	详情	详情
(IV)	43775	6-chloro-5-(methylsulfanyl)indoline; 6-chloro-2,3-dihydro-1H-indol-5-yl methyl sulfide		C₉H₁₀ClNS	详情	详情

Extended Information