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【结 构 式】 
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【分子编号】28130 【品名】tert-butyl (4S,5S)-5-((2S)-2-[[(3-amino-2,2-dimethyl-3-oxopropyl)amino]carbonyl]-3-methylbutyl)-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C38H65N3O8 【 分 子 量 】691.94952 【元素组成】C 65.96% H 9.47% N 6.07% O 18.5% |
与该中间体有关的原料药合成路线共 2 条
合成路线1
该中间体在本合成路线中的序号：(XX)This alcohol is oxidized to aldehyde with NMMO and tetrapropylammonium perruthenate (TPAP), and further oxidized to carboxylic acid (XVIII) with KMnO4 and tetrabutylammonium bromide (TBAB). Coupling of (XVIII) with aminoamide (XIX) by means of diethyl cyanophosphonate and TEA gives (XX). Finally, acid hydrolysis of the oxazolidine ring and Boc protecting groups of (XX) furnishes the corresponding amino alcohol, which is finally converted to the hemifumarate salt.
| 【1】 Mealy, N.E.; Castañer, R.M.; Silvestre, J.S.; Castañer, J.; Aliskiren Fumarate. Drugs Fut 2001, 26, 12, 1139. |
| 【2】 Rigollier, P.; Stutz, S.; Goeschke, R.; Yamaguchi, Y.; Maibaum, J.; Wood, J.; Structural modification of the P2' position of 2,7-dialkyl substituted 5(S)-amino-4(S)-hydroxy-8-phenyl-octane-carboxamides: Discovery of a potent non-peptide renin inhibitor active after once daily dosing in marmosets. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.230. |
| 【3】 Göschke, R.; Maibaum, J.K.; Schilling, W.; Stutz, S.; Rigollier, P.; Yamaguchi, Y.; Cohen, N.C.; Herold, P. (Novartis AG); Delta-amino-gamma-hydroxy-omega-aryl alkanoic acid amides with enzyme especially renin inhibiting activities. EP 0678500; EP 0678503; JP 1996053434; JP 1996081430; US 5559111; US 5627182; US 5646143 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 42235 | Diethyl phosphorocyanidate; Diethyl cyanophosphonate; Cyanophosphonic acid diethyl ester; Diethyl phosphoryl cyanide; DEPC | 2942-58-7 | C5H10NO3P | 详情 | 详情 | |
| (XVIII) | 28128 | (2S)-2-[((4S,5S)-3-(tert-butoxycarbonyl)-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidin-5-yl)methyl]-3-methylbutyric acid | C33H55NO8 | 详情 | 详情 | |
| (XIX) | 28129 | 3-amino-2,2-dimethylpropanamide | 324763-51-1 | C5H12N2O | 详情 | 详情 |
| (XX) | 28130 | tert-butyl (4S,5S)-5-((2S)-2-[[(3-amino-2,2-dimethyl-3-oxopropyl)amino]carbonyl]-3-methylbutyl)-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C38H65N3O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)
| 【1】 Maibaum J, Stutz S, Goschke R, et al. 2007. Structural modification of the P2' position of 2,7-dialkyl-substituted 5(S)-amino-4(S)-hydro-8-phenyl-octanecarboxamides: the discovery of aliskiren, a potent nonpeptide human renin inhibitor active after once daily dosing in marmosets. J Med Chem, 50(20): 4832～4844 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 66991 | (R)-((2-(bromomethyl)-3-methylbutoxy)methyl)benzene | C13H19BrO | 详情 | 详情 | |
| (V) | 66992 | C40H63NO7 | 详情 | 详情 | ||
| (VIII) | 28129 | 3-amino-2,2-dimethylpropanamide | 324763-51-1 | C5H12N2O | 详情 | 详情 |
| (I) | 28123 | tert-butyl (1S,3S)-1-formyl-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentylcarbamate | C24H39NO6 | 详情 | 详情 | |
| (III) | 28125 | tert-butyl (1S,4S)-4-[(benzyloxy)methyl]-2-hydroxy-1-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-5-methylhexylcarbamate | C37H59NO7 | 详情 | 详情 | |
| (IV) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (VI) | 28127 | tert-butyl (4S,5S)-5-[(2S)-2-(hydroxymethyl)-3-methylbutyl]-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C33H57NO7 | 详情 | 详情 | |
| (VII) | 28128 | (2S)-2-[((4S,5S)-3-(tert-butoxycarbonyl)-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidin-5-yl)methyl]-3-methylbutyric acid | C33H55NO8 | 详情 | 详情 | |
| (IX) | 28130 | tert-butyl (4S,5S)-5-((2S)-2-[[(3-amino-2,2-dimethyl-3-oxopropyl)amino]carbonyl]-3-methylbutyl)-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C38H65N3O8 | 详情 | 详情 | |
| (X) | 66994 | tert-butyl (8-((3-amino-2,2-dimethyl-3-oxopropyl)carbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-yl)carbamate | C35H61N3O8 | 详情 | 详情 | |
| (XII) | 28126 | tert-butyl (4S,5S)-5-[(2S)-2-[(benzyloxy)methyl]-3-methylbutyl]-4-[(2S)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C40H63NO7 | 详情 | 详情 |
Extended Information