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【结 构 式】

【分子编号】52460

【品名】1-({2-[5-(1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-3-phenylpropyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-4-phenylbutanoyl}oxy)-2,5-pyrrolidinedione

【CA登记号】

【 分 子 式 】C33H36N2O10

【 分 子 量 】620.65632

【元素组成】C 63.86% H 5.85% N 4.51% O 25.78%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

The oxidation of the chiral 2(R)-(benzyloxymethyl-4-phenyl-1-butanol (I) with (COCl)2 and TEA in DMSO/dichloromethane gives the corresponding aldehyde (II) , which by a pinacol coupling promoted by VCl3, Zn and 1,3-dimethylimidazolidin-2-one (DMI) in dichloromethane yields the glycol (III) as a mixture of all the possible enantiomers. The protection of the glycol function of (III) by means of 2,2-dimethoxypropane (IV), 2-methoxypropene and CSA in acetone affords the isopropylidene ketal (V), which is debenzylated by hydrogenation with H2 over Pd/C in aq. NaHCO3/EtOAc to provide the hexane-1,6-diol (VI). The oxidation of diol (VI) with RuCl3 and NaIO4 in acetonitrile/water/dichloromethane gives the adipic acid derivative (VII), which is treated with disuccinimidyl carbonate (VIII) to yield the corresponding enantiomeric mixture of activated esters, which is resolved by column chromatography to isolate the (R,R)-activated ester (IX). The reaction of (IX) with (1S,2R)-1-amino-2-indanol (X) in hot dichloroethane (DCE) affords the diamide (XI), which is finally deprotected (elimination of the isopropylidene group) by means of FeCl3.6H2O in dichloromethane to provide the target (R,R,R,R)-dihydroxydiamide.

1 Muhlman, A.; et al.; Synthesis of novel potent, diol-based HIV-1 protease inhibitors via intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal. J Med Chem 2001, 44, 21, 3407.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(R,R)-(III) 52454 1,8-diphenyl-3,6-bis{[(phenylmethyl)oxy]methyl}-4,5-octanediol C36H42O4 详情 详情
(R,S)-(III) 52455 1,8-diphenyl-3,6-bis{[(phenylmethyl)oxy]methyl}-4,5-octanediol C36H42O4 详情 详情
(S,S)-(III) 52456 1,8-diphenyl-3,6-bis{[(phenylmethyl)oxy]methyl}-4,5-octanediol C36H42O4 详情 详情
(I) 52452 4-phenyl-2-{[(phenylmethyl)oxy]methyl}-1-butanol C18H22O2 详情 详情
(II) 52453 4-phenyl-2-{[(phenylmethyl)oxy]methyl}butanal C18H20O2 详情 详情
(IV) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(V) 52457 2,2-dimethyl-4,5-bis(3-phenyl-1-{[(phenylmethyl)oxy]methyl}propyl)-1,3-dioxolane; 2-[2,2-dimethyl-5-(3-phenyl-1-{[(phenylmethyl)oxy]methyl}propyl)-1,3-dioxolan-4-yl]-4-phenylbutyl phenylmethyl ether C39H46O4 详情 详情
(VI) 52458   C25H34O4 详情 详情
(VII) 52459   C25H30O6 详情 详情
(VIII) 20417 1-([[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]oxy)-2,5-pyrrolidinedione 74124-79-1 C9H8N2O7 详情 详情
(IX) 52460 1-({2-[5-(1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-3-phenylpropyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-4-phenylbutanoyl}oxy)-2,5-pyrrolidinedione C33H36N2O10 详情 详情
(X) 16239 (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol; Cis-(1S)-1-amino-2,3-dihydro-1H-inden-2-ol 126456-43-7 C9H11NO 详情 详情
(XI) 52461   C43H48N2O6 详情 详情
Extended Information