(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]-1-ethanamine; (1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethylamine -Drug Synthesis Database

【结构式】

【分子编号】58608

【品名】(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]-1-ethanamine; (1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethylamine

【CA登记号】

【分子式】C₂₈H₃₅NO₅Si

【分子量】493.67514

【元素组成】C 68.12% H 7.15% N 2.84% O 16.2% Si 5.69%

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：(VIII)

Synthesis of the amine intermediate (VIII): The condensation of 1,3-benzodioxole (I) with the didehydro morpholinone (II) by means of TFA in dichloromethane gives the chiral adduct (III), which is treated with Tf2O and pyridine in dichloromethane to yield the triflate (IV). The reductive cleavage of (IV) by means of NaBH4 in methanol affords the aminodiol (V), which is selectively monosilylated at the primary OH group with Tbdps-Cl and imidazole to provide the silyl ether (VI). The reaction of the triflate group of (VI) with MeZnCl and PdCl2(dppf) in refluxing THF gives the methylated compound (VII), which is treated with Pb(OAc)4 and NH2OH in ethanol to afford the target primary amine intermediate (VIII).

参考文献中间体

合成目标

【1】 Abe, M.; Yanagisawa, A.; Tohma, S.; Kan, T.; Fukuyama, T.; Endo, A.; Total synthesis of ecteinascidin 743. J Am Chem Soc 2002, 124, 23, 6552.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	58601	5-(methoxymethoxy)-1,3-benzodioxol-4-ol	C₉H₁₀O₅	详情	详情
(II)	58602	(5R)-6,6-dimethyl-5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one	C₁₂H₁₃NO₂	详情	详情
(III)	58603	(3R,5R)-3-[7-hydroxy-6-(methoxymethoxy)-1,3-benzodioxol-4-yl]-6,6-dimethyl-5-phenyl-2-morpholinone	C₂₁H₂₃NO₇	详情	详情
(IV)	58604	7-[(3R,5R)-6,6-dimethyl-2-oxo-5-phenylmorpholinyl]-5-(methoxymethoxy)-1,3-benzodioxol-4-yl trifluoromethanesulfonate	C₂₂H₂₂F₃NO₉S	详情	详情
(V)	58605	7-((1R)-2-hydroxy-1-{[(1R)-2-hydroxy-2-methyl-1-phenylpropyl]amino}ethyl)-5-(methoxymethoxy)-1,3-benzodioxol-4-yl trifluoromethanesulfonate	C₂₂H₂₆F₃NO₉S	详情	详情
(VI)	58606	7-((1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-{[(1R)-2-hydroxy-2-methyl-1-phenylpropyl]amino}ethyl)-5-(methoxymethoxy)-1,3-benzodioxol-4-yl trifluoromethanesulfonate	C₃₈H₄₄F₃NO₉SSi	详情	详情
(VII)	58607	(1R)-1-({(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}amino)-2-methyl-1-phenyl-2-propanol	C₃₈H₄₇NO₆Si	详情	详情
(VIII)	58608	(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]-1-ethanamine; (1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethylamine	C₂₈H₃₅NO₅Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The condensation of the amine intermediate (VIII) with iodo-L-phenylalanine intermediate (XVII), 4-methoxyphenyl isocyanide (XVIII) and acetaldehyde (XIX) in refluxing methanol gives the adduct (XX), which is desilylated with TBAF in THF and acylated with Ac2O and pyridine to yield the acetoxy derivative (XXI). Elimination of the Mom and Boc protecting groups of (XXI) by means of TFA in dichloromethane affords the aminophenol (XXII), which is submitted to cyclization in refluxing ethyl acetate to provide the piperazinedione derivative (XXIII). The reaction of the OH group of (XXIII) with MsCl and pyridine in dichloromethane and the piperazine NH with Boc2O and DMAP in acetonitrile gives the fully protected compound (XXIV), which is reduced with NaBH4 in EtOH/dichloromethane and dehydrated by means of CSA and quinoline in refluxing toluene to yield the tetrahydropyrazinone (XXV). The cyclization of (XXV) by means of Pd2(dba)3, P(o-tol)3 and TEA in refluxing acetonitrile affords the tricyclic compound (XXVI).

参考文献中间体

合成目标

【1】 Abe, M.; Yanagisawa, A.; Tohma, S.; Kan, T.; Fukuyama, T.; Endo, A.; Total synthesis of ecteinascidin 743. J Am Chem Soc 2002, 124, 23, 6552.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	58608	(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]-1-ethanamine; (1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethylamine		C₂₈H₃₅NO₅Si	详情	详情
(XVII)	58616	(2S)-3-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylphenyl]-2-[(tert-butoxycarbonyl)amino]propanoic acid		C₂₃H₂₈INO₆	详情	详情
(XVIII)	58617	4-methoxy-N-methyleneaniline; N-(4-methoxyphenyl)-N-methyleneamine		C₈H₉NO	详情	详情
(XIX)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(XX)	58618	tert-butyl (1S)-1-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylbenzyl]-2-{{(1R)-2-{[tert-butyl(diphenyl)silyl]oxy}-1-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}[2-(4-methoxyanilino)-1-methyl-2-oxoethyl]amino}-2-oxoethylcarbamate		C₆₁H₇₂IN₃O₁₂Si	详情	详情
(XXI)	58619	(2R)-2-{{(2S)-3-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylphenyl]-2-[(tert-butoxycarbonyl)amino]propanoyl}[2-(4-methoxyanilino)-1-methyl-2-oxoethyl]amino}-2-[6-(methoxymethoxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl acetate		C₄₇H₅₆IN₃O₁₃	详情	详情
(XXII)	58620	(2R)-2-{{(2S)-2-amino-3-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylphenyl]propanoyl}[2-(4-methoxyanilino)-1-methyl-2-oxoethyl]amino}-2-(6-hydroxy-7-methyl-1,3-benzodioxol-4-yl)ethyl acetate		C₄₀H₄₄IN₃O₁₀	详情	详情
(XXIII)	58621	(2R)-2-{(3S)-3-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylbenzyl]-6-methyl-2,5-dioxopiperazinyl}-2-(6-hydroxy-7-methyl-1,3-benzodioxol-4-yl)ethyl acetate		C₃₃H₃₅IN₂O₉	详情	详情
(XXIV)	58622	tert-butyl (2S)-4-((1R)-2-(acetyloxy)-1-{7-methyl-6-[(methylsulfonyl)oxy]-1,3-benzodioxol-4-yl}ethyl)-2-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylbenzyl]-5-methyl-3,6-dioxo-1-piperazinecarboxylate		C₃₉H₄₅IN₂O₁₃S	详情	详情
(XXV)	58623	tert-butyl (2S)-4-((1R)-2-(acetyloxy)-1-{7-methyl-6-[(methylsulfonyl)oxy]-1,3-benzodioxol-4-yl}ethyl)-2-[3-(benzyloxy)-2-iodo-4-methoxy-5-methylbenzyl]-5-methyl-3-oxo-3,4-dihydro-1(2H)-pyrazinecarboxylate		C₃₉H₄₅IN₂O₁₂S	详情	详情
(XXVI)	58624	tert-butyl (1R,9S)-11-((1R)-2-(acetyloxy)-1-{7-methyl-6-[(methylsulfonyl)oxy]-1,3-benzodioxol-4-yl}ethyl)-3-(benzyloxy)-4-methoxy-5-methyl-12-methylene-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate		C₃₉H₄₄N₂O₁₂S	详情	详情

Extended Information