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【结 构 式】 
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【分子编号】50673 【品名】tert-butyl 2-[4-(3-[[1-(4-methoxybenzyl)-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl]amino]-2-[[2-methyl-2-(2-naphthyl)propanoyl]amino]-3-oxopropyl)phenyl]-2-methylpropanoate 【CA登记号】 |
【 分 子 式 】C45H51N3O6 【 分 子 量 】729.91656 【元素组成】C 74.05% H 7.04% N 5.76% O 13.15% |
合成路线1
该中间体在本合成路线中的序号：(XX)Alkylation of 4-methyl-3-nitro-2-pyridone (XIV) with p-methoxybenzyl chloride (XV) gave the N-benzylpyridone (XVI). The nitro group of (XVI) was then reduced to amine (XVII) by catalytic hydrogenation over Pd/C. Coupling of the intermediate amino acid derivative (XIII) with the aminopyridone (XVII) provided amide (XVIII). Selective cleavage of the N-Boc group of (XVIII) in the presence of the tert-butyl ester was achieved by treatment with HCl in dioxan. The resultant amine (XIX) was then coupled with 2,2-dimethyl-(2-naphthyl)acetic acid (IV) to furnish amide (XX). Finally, the title (S)-carboxylic acid was obtained by tert-butyl ester cleavage with trifluoroacetic acid followed by separation of the racemic mixture by means of chiral HPLC.
| 【1】 Proudfoot, J.R.; et al.; Nonpeptidic, monocharged, cell permeable ligands of the p56lck SH2 domain. J Med Chem 2001, 44, 15, 2421. |
| 【2】 Betageri, R.; Llinas-Brunet, M.; Moss, N.; Patel, U.; Cardozo, M.; Beaulieu, P.L.; Ferland, J.-M.; Proudfoot, J.R. (Boehringer Ingelheim Pharmaceuticals Inc.); Pyridones as Src family SH2 domain inhibitors. EP 1045836; US 6054470; US 6156784; WO 9931066 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 50660 | 2-methyl-2-(2-naphthyl)propionic acid | C14H14O2 | 详情 | 详情 | |
| (XIII) | 50667 | N-(tert-butoxycarbonyl)-4-[2-(tert-butoxy)-1,1-dimethyl-2-oxoethyl]phenylalanine | C22H33NO6 | 详情 | 详情 | |
| (XIV) | 50668 | 4-Methyl-3-nitro-2-pyridone | C6H6N2O3 | 详情 | 详情 | |
| (XV) | 11910 | 4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether | 824-94-2 | C8H9ClO | 详情 | 详情 |
| (XVI) | 50669 | 1-(4-methoxybenzyl)-4-methyl-3-nitro-2(1H)-pyridinone | C14H14N2O4 | 详情 | 详情 | |
| (XVII) | 50670 | 3-amino-1-(4-methoxybenzyl)-4-methyl-2(1H)-pyridinone | C14H16N2O2 | 详情 | 详情 | |
| (XVIII) | 50671 | tert-butyl 2-[4-(2-[(tert-butoxycarbonyl)amino]-3-[[1-(4-methoxybenzyl)-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl]amino]-3-oxopropyl)phenyl]-2-methylpropanoate | C36H47N3O7 | 详情 | 详情 | |
| (XIX) | 50672 | tert-butyl 2-[4-(2-amino-3-[[1-(4-methoxybenzyl)-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl]amino]-3-oxopropyl)phenyl]-2-methylpropanoate | C31H39N3O5 | 详情 | 详情 | |
| (XX) | 50673 | tert-butyl 2-[4-(3-[[1-(4-methoxybenzyl)-4-methyl-2-oxo-1,2-dihydro-3-pyridinyl]amino]-2-[[2-methyl-2-(2-naphthyl)propanoyl]amino]-3-oxopropyl)phenyl]-2-methylpropanoate | C45H51N3O6 | 详情 | 详情 |