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【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 CAS号 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