|
【结 构 式】 
|
【分子编号】38798 【品名】2-chloro-4,6-dimethoxy-1,3,5-triazine; 4-chloro-6-methoxy-1,3,5-triazin-2-yl methyl ether 【CA登记号】3140-73-6 |
【 分 子 式 】C5H6ClN3O2 【 分 子 量 】175.57436 【元素组成】C 34.2% H 3.44% Cl 20.19% N 23.93% O 18.23% |
合成路线1
该中间体在本合成路线中的序号：(IX)Alkylation of diethyl acetamidomalonate (I) with 1-bromo-3-phenylpropane (II) in the presence of NaOEt afforded phenylpropyl malonate (III). Hydrolysis and subsequent decarboxylation of malonate ester (III) yielded racemic 2-(acetylamino)-5-phenylpentanoic acid (IV). Kinetic resolution was achieved by enantioselective hydrolysis of the (S)-acetamide to give amino acid (VI). The desired (R)-enantiomer (V) was then hydrolyzed with HCl and further esterified with HCl-EtOH to provide amino ester (VII). Coupling with N-Boc-alpha-aminoisobutyric acid (VIII) via activation with 2-chloro-4,6-dimethoxy-1,3,5-triazine (IX) furnished dipeptide (X). The ethyl ester group of (X) was then hydrolyzed to acid (XI) using LiOH.
| 【1】 Growth hormone secretagogues. EP 0933365; WO 9908699 . |
| 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) | 16710 | Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate | 1068-90-2 | C9H15NO5 | 详情 | 详情 |
| (II) | 20884 | 1-(3-bromopropyl)benzene | 637-59-2 | C9H11Br | 详情 | 详情 |
| (III) | 35758 | diethyl 2-(acetamido)-2-(3-phenylpropyl)malonate | C18H25NO5 | 详情 | 详情 | |
| (IV) | 38799 | N-acetyl-5-phenylnorvaline | C13H17NO3 | 详情 | 详情 | |
| (V) | 35759 | (2R)-2-(acetamido)-5-phenylpentanoic acid | C13H17NO3 | 详情 | 详情 | |
| (VI) | 35760 | (2S)-2-amino-5-phenylpentanoic acid | C11H15NO2 | 详情 | 详情 | |
| (VII) | 35761 | ethyl (2R)-2-amino-5-phenylpentanoate | C13H19NO2 | 详情 | 详情 | |
| (VIII) | 18471 | N-(tert-butoxycarbonyl)-2-methylalanine | 30992-29-1 | C9H17NO4 | 详情 | 详情 |
| (IX) | 38798 | 2-chloro-4,6-dimethoxy-1,3,5-triazine; 4-chloro-6-methoxy-1,3,5-triazin-2-yl methyl ether | 3140-73-6 | C5H6ClN3O2 | 详情 | 详情 |
| (X) | 35762 | ethyl (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoate | C22H34N2O5 | 详情 | 详情 | |
| (XI) | 18473 | (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid | C20H30N2O5 | 详情 | 详情 |