GL-406349, -Drug Synthesis Database

【结构式】

【药物名称】GL-406349

【化学名称】N,N'-Bis[2-[N-[2-(N2,N5-dimethyl-DL-lysylamino)ethyl]carbamoyl]-1H-indol-6-yl]-1H -indole-2,5-dicarboxamide

【CA登记号】

【分子式】C₄₆H₅₉N₁₃O₆

【分子量】890.06663

【开发单位】Genelabs (Originator)

【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY

合成路线1 合成路线2

合成路线1

Reaction of methyl 6-nitroindole-2-carboxylate (I) with ethylenediamine (II) in hot DMF gives amino amide (III). After protection of (III) as the N-Boc derivative (IV), catalytic hydrogenation of its nitro group affords amine (V). Indole-2,5-dicarboxylic (VI) is activated as the bis-pentafluorophenyl ester (VII) by treatment with pentafluorophenyl trifluoroacetate. Subsequent coupling between the bis-pentafluorophenyl ester (VII) and amino indole (V) furnishes diamide (VIII). Removal of the N-Boc groups using trifluoroacetic acid in the presence of anisole produces diamine (IX).

参考文献中间体

【1】 Roberts, C.; et al.; Discovery af a new class of broad-spectrum antifungal compounds that target the minor groove of DNA. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 67.

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)	56422	methyl 6-nitro-1H-indole-2-carboxylate		C₁₀H₈N₂O₄	详情	详情
(II)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(III)	56423	N-(2-aminoethyl)-6-nitro-1H-indole-2-carboxamide		C₁₁H₁₂N₄O₃	详情	详情
(IV)	56424	tert-butyl 2-{[(6-nitro-1H-indol-2-yl)carbonyl]amino}ethylcarbamate		C₁₆H₂₀N₄O₅	详情	详情
(V)	56425	tert-butyl 2-{[(6-amino-1H-indol-2-yl)carbonyl]amino}ethylcarbamate		C₁₆H₂₂N₄O₃	详情	详情
(VI)	56426	1H-indole-2,5-dicarboxylic acid		C₁₀H₇NO₄	详情	详情
(VII)	56427	bis(2,3,4,5,6-pentafluorophenyl) 1H-indole-2,5-dicarboxylate		C₂₂H₅F₁₀NO₄	详情	详情
(VIII)	56428	tert-butyl 2-[({6-[({2-[({2-[({2-[(tert-butoxycarbonyl)amino]ethyl}amino)carbonyl]-1H-indol-6-yl}amino)carbonyl]-1H-indol-5-yl}carbonyl)amino]-1H-indol-2-yl}carbonyl)amino]ethylcarbamate		C₄₂H₄₇N₉O₈	详情	详情
(IX)	56429	N~2~,N~5~-bis(2-{[(2-aminoethyl)amino]carbonyl}-1H-indol-6-yl)-1H-indole-2,5-dicarboxamide		C₃₂H₃₁N₉O₄	详情	详情

合成路线2

Coupling of diamine (IX) with the Boc-protected diamino acid (X) by means of DCC and HOBt gives rise to amide (XI). The title compound is finally obtained by acidic cleavage of the N-Boc protecting groups of (XI).

参考文献中间体

【1】 Roberts, C.; et al.; Discovery af a new class of broad-spectrum antifungal compounds that target the minor groove of DNA. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 67.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	54629	benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate	C₁₅H₂₁NO₃	详情	详情
(X)	54630	tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate	C₂₁H₃₃NO₅	详情	详情
(XI)	54631	(1S)-2-hydroxy-1,2,2-triphenylethyl propionate	C₂₃H₂₂O₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)