Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine -Drug Synthesis Database

【结构式】

【分子编号】40537

【品名】Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine

【CA登记号】61-54-1

【分子式】C₁₀H₁₂N₂

【分子量】160.21876

【元素组成】C 74.97% H 7.55% N 17.48%

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：(VIII)

Oxidation of 5-hydroxy-5,6,7,8-tetrahydroisoquinoline (I) using CrO3 in pyridine produced the corresponding ketone (II). Subsequent condensation of (II) with methyl cyanoformate (A) in the presence of lithium hexamethyldisilazide gave ketoester (III), which was reduced to hydroxyester (IV) by means of catalytic hydrogenation. Dehydration of (IV) to the unsaturated ester (V) was achieved by treatment with methanesulfonyl chloride and triethylamine, followed by basic elimination with DBU. Saponification of the ester group of (V) produced carboxylic acid (VI). After activation of (VI) as the mixed anhydride (VII) with isopropyl chloroformate (B), coupling with tryptamine (VIII) furnished the title amide, which was finally isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 May, S.; Chan, L.; Chen, Y.; Jin, H.; Hu, Z.; Bedard, J.; Stefanac, T.; Turcotte, N.; Design and evaluation of dihydroisoquinolines as potent and orally bioavailable human cytomegalovirus inhibitors. Bioorg Med Chem Lett 2000, 10, 13, 1477.
【2】 Bedard, J.; Rando, R.; Falardeau, G.; Lavallee, J.-F. (BioChem Pharma Inc.); Antiviral cpds.. WO 9929318 .

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)	18001	methyl 2-nitriloacetate; carbonocyanic acid, methyl ester	17640-15-2	C₃H₃NO₂	详情	详情
(B)	26492	2-[(chlorocarbonyl)oxy]propane	108-23-6	C₄H₇ClO₂	详情	详情
(I)	40530	5,6,7,8-tetrahydro-5-isoquinolinol		C₉H₁₁NO	详情	详情
(II)	40531	7,8-dihydro-5(6H)-isoquinolinone		C₉H₉NO	详情	详情
(III)	40532	methyl 5-hydroxy-7,8-dihydro-6-isoquinolinecarboxylate		C₁₁H₁₁NO₃	详情	详情
(IV)	40533	methyl 5-hydroxy-5,6,7,8-tetrahydro-6-isoquinolinecarboxylate		C₁₁H₁₃NO₃	详情	详情
(V)	40534	methyl 7,8-dihydro-6-isoquinolinecarboxylate		C₁₁H₁₁NO₂	详情	详情
(VI)	40535	7,8-dihydro-6-isoquinolinecarboxylic acid		C₁₀H₉NO₂	详情	详情
(VII)	40536			C₁₄H₁₅NO₄	详情	详情
(VIII)	40537	Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine	61-54-1	C₁₀H₁₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The esterification of 4-formylcinnamic acid (I) with methanol and HCl gives the methyl ester (II), which can be obtained by Heck coupling of 4-bromobenzaldehyde (III) with methyl acrylate (IV). The reductocondensation of (II) with tryptamine (V) by means of NaBH(OAc)3 in dichloroethane yields the secondary amine (VI), which is alkylated with 2-(tert-butyldimethylsilyloxy)ethyl bromide (VII) by means of DIEA in DMSO to afford the tertiary amine (VIII). The reaction of the methyl ester group of (VIII) with KOH and hydroxylamine in methanol provides the silylated hydroxamic acid (IX), which is finally deprotected with TFA in water.

参考文献中间体

合成目标

【1】 Perez, L.B.; Remiszewski, S.; Sambucetti, L.; et al.; Discovery and SAR of NVP-LAQ824, a novel histone deacetylase inhibitor with in vitro and in vivo antitumor activity. Proc Am Assoc Cancer Res 2002, 43, Abst 3671.
【2】 Bair, K.W.; Versace, R.W.; Green, M.A.; Remiszewski, S.W.; Perez, L.B.; Sambucetti, L.; Sharma, S.K. (Novartis AG; Novartis-Erfindungen VmbH); Deacetylase inhibitors. WO 0222577 .

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)	55571	4-Formylcinnamic acid	23359-08-2	C₁₀H₈O₃	详情	详情
(II)	46515	methyl (E)-3-(4-formylphenyl)-2-propenoate	7560-50-1	C₁₁H₁₀O₃	详情	详情
(III)	22231	4-Bromobenzaldehyde	1122-91-4	C₇H₅BrO	详情	详情
(IV)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(V)	40537	Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine	61-54-1	C₁₀H₁₂N₂	详情	详情
(VI)	55572	methyl 3-[4-({[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-2-propenoate		C₂₁H₂₂N₂O₂	详情	详情
(VII)	55573	2-Bromoethoxy-t-butyldimethylsilane	86864-60-0	C₈H₁₉BrOSi	详情	详情
(VIII)	55574			C₂₉H₄₀N₂O₃Si	详情	详情
(IX)	55575	3-[4-({(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-N-hydroxy-2-propenamide		C₂₈H₃₉N₃O₃Si	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

2-Aminothiazole (I) is coupled to 3-fluorosulfonylphenyl isocyanate (II) producing the diaryl urea (III). Subsequent reaction of sulfonyl fluoride (III) with tryptamine (IV) in hot acetonitrile furnishes the target sulfonamide.

参考文献中间体

合成目标

【1】 Beyer, D.; Kroll, H.; Bauser, M.; Siegel, S.; Brotz, H.; Endermann, R.; Schiffer, G.; Ziegelbauer, K.; Habich, D.; Pohlmann, J.; Phenyl-thiazolylurea-sulfonamides as novel inhibitors of phenylalanine-tRNA synthetase. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-756.

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)	19795	2-Thiazolamine; 1,3-thiazol-2-amine; 1,3-thiazol-2-ylamine	96-50-4	C₃H₄N₂S	详情	详情
(II)	64472	3-isocyanatobenzenesulfonyl fluoride		C₇H₄FNO₃S	详情	详情
(III)	64473	3-{[(1,3-thiazol-2-ylamino)carbonyl]amino}benzenesulfonyl fluoride		C₁₀H₈FN₃O₃S₂	详情	详情
(IV)	40537	Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine	61-54-1	C₁₀H₁₂N₂	详情	详情

Extended Information