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【结 构 式】 
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【分子编号】52336 【品名】1-[1-({2-[5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetyl}amino)-2-phenylethyl]-2-oxo-5-(2-pyridinyloxy)pentyl acetate 【CA登记号】 |
【 分 子 式 】C37H41N5O8 【 分 子 量 】683.76144 【元素组成】C 64.99% H 6.04% N 10.24% O 18.72% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Alkylation of 2-hydroxypyridine (XI) with bromide (X) produced a mixture of the N-alkylated pyridone (XII) and the pyridyl ether (XIII), which were separated by column chromatography. The required minor regioisomer (XIII) was desilylated with tetrabutylammonium fluoride, and the resultant alcohol (XIV) was oxidized under Swern conditions to the ketone (XV). Acidic hydrolysis of the cyclic aminal function of (XV) furnished amino alcohol (XVI). This was then coupled with the pyrimidinylacetic acid (XVII) to yield amide (XVIII). The free hydroxyl group of (XVIII) was subsequently esterified with acetic anhydride giving ester (XIX).
| 【1】 Doggrell, S.A.; Castaner, J.; NK-3201. Drugs Fut 2003, 28, 4, 323. |
| 【2】 Suzuki, Y.; Ishida, K. (Nippon Kayaku Co., Ltd.); Novel acetamide derivs. and protease inhibitors. EP 0936216; US 6271238; WO 9809949 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 52326 | 1,1-dimethylethyl 5-(4-bromo-1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}butyl)-2,2-dimethyl-4-(phenylmethyl)-1,3-oxazolidine-3-carboxylate | C27H46BrNO4Si | 详情 | 详情 | |
| (XI) | 52328 | 2-pyridinol | C5H5NO | 详情 | 详情 | |
| (XII) | 52329 | 1,1-dimethylethyl 5-{1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4-[2-oxo-1(2H)-pyridinyl]butyl}-2,2-dimethyl-4-(phenylmethyl)-1,3-oxazolidine-3-carboxylate | C32H50N2O5Si | 详情 | 详情 | |
| (XIII) | 52330 | 1,1-dimethylethyl 5-[1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4-(2-pyridinyloxy)butyl]-2,2-dimethyl-4-(phenylmethyl)-1,3-oxazolidine-3-carboxylate | C32H50N2O5Si | 详情 | 详情 | |
| (XIV) | 52331 | 1,1-dimethylethyl 5-[1-hydroxy-4-(2-pyridinyloxy)butyl]-2,2-dimethyl-4-(phenylmethyl)-1,3-oxazolidine-3-carboxylate | C26H36N2O5 | 详情 | 详情 | |
| (XV) | 52332 | 1,1-dimethylethyl 2,2-dimethyl-4-(phenylmethyl)-5-[4-(2-pyridinyloxy)butanoyl]-1,3-oxazolidine-3-carboxylate | C26H34N2O5 | 详情 | 详情 | |
| (XVI) | 52333 | 2-amino-3-hydroxy-1-phenyl-7-(2-pyridinyloxy)-4-heptanone | C18H22N2O3 | 详情 | 详情 | |
| (XVII) | 52334 | 2-[5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetic acid | C17H19N3O5 | 详情 | 详情 | |
| (XVIII) | 52335 | 1,1-dimethylethyl 1-(2-{[2-hydroxy-3-oxo-1-(phenylmethyl)-6-(2-pyridinyloxy)hexyl]amino}-2-oxoethyl)-6-oxo-2-phenyl-1,6-dihydro-5-pyrimidinylcarbamate | C35H39N5O7 | 详情 | 详情 | |
| (XIX) | 52336 | 1-[1-({2-[5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetyl}amino)-2-phenylethyl]-2-oxo-5-(2-pyridinyloxy)pentyl acetate | C37H41N5O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIX)Acidic Boc group cleavage from (XIX) produced amine (XX). This was converted to formamide (XXI) upon treatment with in situ-generated formic acetic anhydride. Selective hydrolysis of the acetate ester of (XXI) was then achieved by treatment with K2CO3 in MeOH. The resultant keto alcohol (XXII) was finally oxidized to the title diketone employing DMSO in the presence of EDC and pyridinium trifluoroacetate
| 【1】 Doggrell, S.A.; Castaner, J.; NK-3201. Drugs Fut 2003, 28, 4, 323. |
| 【2】 Suzuki, Y.; Ishida, K. (Nippon Kayaku Co., Ltd.); Novel acetamide derivs. and protease inhibitors. EP 0936216; US 6271238; WO 9809949 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIX) | 52336 | 1-[1-({2-[5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetyl}amino)-2-phenylethyl]-2-oxo-5-(2-pyridinyloxy)pentyl acetate | C37H41N5O8 | 详情 | 详情 | |
| (XX) | 52337 | 1-[1-({2-[5-amino-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetyl}amino)-2-phenylethyl]-2-oxo-5-(2-pyridinyloxy)pentyl acetate | C32H33N5O6 | 详情 | 详情 | |
| (XXI) | 52338 | 1-[1-({2-[5-(formylamino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]acetyl}amino)-2-phenylethyl]-2-oxo-5-(2-pyridinyloxy)pentyl acetate | C33H33N5O7 | 详情 | 详情 | |
| (XXII) | 52339 | 2-[5-(formylamino)-6-oxo-2-phenyl-1(6H)-pyrimidinyl]-N-[2-hydroxy-3-oxo-1-(phenylmethyl)-6-(2-pyridinyloxy)hexyl]acetamide | C31H31N5O6 | 详情 | 详情 |