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【结 构 式】 
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【分子编号】47935 【品名】tert-butyl (2S,4S)-4-(4-bromobenzyl)-4-methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C22H24BrNO4 【 分 子 量 】446.3409 【元素组成】C 59.2% H 5.42% Br 17.9% N 3.14% O 14.34% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of N-(tert-butoxycarbonyl)-L-alanine (I) with benzaldehyde dimethylacetal (II) by means of SOCl2 and ZnCl2 gives the oxazolidinone (III), which is alkylated with 4-bromobenzyl bromide (IV) and KHMDS in THF to yield the alkylated compound (V). The opening of the oxazolidinone ring of (V) with HBr/HOAc, followed by esterification with EtOH/HCl, affords the aminopropionic ester (VI), which is cyclized again with 3,5-dichlorophenyl isocyanate (VII) by means of Na2CO3 to provide imidazolidinedione (VIII). Finally, this compound is methylated with Me-I and NaHMDS to give the target compound.
| 【1】 Kapadia, S.R.; et al.; An improved synthesis of chiral alpha-(4-bromobenzyl)alanine ethyl ester and its application to the synthesis of LFA-1 antagonist BIRT-377. J Org Chem 2001, 66, 5, 1903. |
| 【2】 Emeigh, J.E.; et al.; Small molecule antagonists of LFA-1 mediated cell adhesion. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 256. |
| 【3】 Bormann, B.J.; Frye, L.L.; Wu, J.-P.; Kelly, T.A. (Boehringer Ingelheim Pharmaceuticals Inc.); Small molecules useful in the treatment of inflammatory disease. EP 0966447; WO 9839303 . |
| 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) | 26450 | Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid | 15761-38-3 | C8H15NO4 | 详情 | 详情 |
| (II) | 27515 | Methoxy(phenyl)methyl methyl ether; Dimethylacetal benzaldehyde; Benzaldehyde dimethylacetal | 1125-88-8 | C9H12O2 | 详情 | 详情 |
| (III) | 47934 | tert-butyl (2S,4S)-4-methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate | C15H19NO4 | 详情 | 详情 | |
| (IV) | 16109 | 1-bromo-4-(bromomethyl)benzene; 4-Bromobenzyl bromide | 589-15-1 | C7H6Br2 | 详情 | 详情 |
| (V) | 47935 | tert-butyl (2S,4S)-4-(4-bromobenzyl)-4-methyl-5-oxo-2-phenyl-1,3-oxazolidine-3-carboxylate | C22H24BrNO4 | 详情 | 详情 | |
| (VI) | 47936 | ethyl (2S)-2-amino-3-(4-bromophenyl)-2-methylpropanoate | C12H16BrNO2 | 详情 | 详情 | |
| (VII) | 47937 | 1,3-dichloro-5-isocyanatobenzene; 3,5-dichlorophenyl isocyanate | C7H3Cl2NO | 详情 | 详情 | |
| (VIII) | 47933 | (5R)-5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methyl-2,4-imidazolidinedione | C17H13BrCl2N2O2 | 详情 | 详情 |