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【结 构 式】 
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【分子编号】27212 【品名】benzyl 2-oxo-6-propyl-1,2-dihydro-3-pyridinylcarbamate 【CA登记号】 |
【 分 子 式 】C16H18N2O3 【 分 子 量 】286.3306 【元素组成】C 67.12% H 6.34% N 9.78% O 16.76% |
合成路线1
该中间体在本合成路线中的序号：(VI)The cyclization of acetyl cyclopropane (I) with 2-nitroacetamide (II) and formamide dimethylacetal (III) by means of p-tolulenesulfonic acid gives the nitro-pyridinone (IV) (1), which is reduced with H2 over Pd/C affording 3-amino-6-propylpyridin-2(1H)-one (V). The protection of the amino group of (V) with benzyl chloroformate affords the carbamate (VI), which is condensed with tert-butyl bromoacetate (VII) by means of NaH in THF giving substituted acetate ester (VIII). The deprotection of (VIII) by hydrogenolysis with H2 over Pd/C in ethyl acetate yields intermediate (IX) with a free amino group, which is treated with benzylsulfonyl chloride (X) and pyridine to afford the sulfonamide (XI). Hydrolysis of the ester group of (XI) with HCl in ethyl acetate gives the carboxylic acid (XII), which is condensed with the pyridylmethylamine (XIII) by means of EDC and HOBT to afford the carboxamide (XIV). Finally, this compound is deprotected with HCl as usual.
| 【1】 C6 modification of the pyridinone core of thrombin inhibitor L-374,087 as a means of enhancing its oral absorption. Bioorg Med Chem Lett 1998, 8, 13, 1719. |
| 【2】 Sanderson, P.E.; Naylor-Olsen, A.M.; Dyer, D.L.; Vacca, J.P.; Isaacs, R.C.A.; Dorsey, B.D.; Fraley, M.E. (Merck & Co., Inc.); Pyridinone-thrombin inhibitors. EP 0835109; JP 1999508558; WO 9701338 . |
| 【3】 Dorsey, B.D.; Isaacs, R.C.A.; Sanderson, P.E.; Dyer, D.L.; Naylor-Olsen, A.M.; Fraley, M.E.; Vacca, J.P. (Merck & Co., Inc.); Pyridinone thrombin inhibitors. US 5668289 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
| (I) | 12435 | Acetylcyclopropane; 1-Cyclopropyl-1-ethanone; Cyclopropylmethylketone | 765-43-5 | C5H8O | 详情 | 详情 |
| (II) | 27209 | 2-nitroacetamide | C2H4N2O3 | 详情 | 详情 | |
| (III) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (IV) | 27210 | 6-cyclopropyl-3-nitro-2(1H)-pyridinone | C8H8N2O3 | 详情 | 详情 | |
| (V) | 27211 | 3-amino-6-propyl-2(1H)-pyridinone | C8H12N2O | 详情 | 详情 | |
| (VI) | 27212 | benzyl 2-oxo-6-propyl-1,2-dihydro-3-pyridinylcarbamate | C16H18N2O3 | 详情 | 详情 | |
| (VII) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (VIII) | 27213 | tert-butyl 2-[3-[[(benzyloxy)carbonyl]amino]-2-oxo-6-propyl-1(2H)-pyridinyl]acetate | C22H28N2O5 | 详情 | 详情 | |
| (IX) | 27214 | tert-butyl 2-[3-amino-2-oxo-6-propyl-1(2H)-pyridinyl]acetate | C14H22N2O3 | 详情 | 详情 | |
| (X) | 27215 | phenylmethanesulfenyl chloride | C7H7ClS | 详情 | 详情 | |
| (XI) | 27216 | tert-butyl 2-[3-[(benzylsulfonyl)amino]-2-oxo-6-propyl-1(2H)-pyridinyl]acetate | C21H28N2O5S | 详情 | 详情 | |
| (XII) | 27217 | 2-[3-[(benzylsulfonyl)amino]-2-oxo-6-propyl-1(2H)-pyridinyl]acetic acid | C17H20N2O5S | 详情 | 详情 | |
| (XIII) | 27218 | tert-butyl 5-(aminomethyl)-6-methyl-2-pyridinylcarbamate | C12H19N3O2 | 详情 | 详情 | |
| (XIV) | 27219 | tert-butyl 5-[([2-[3-[(benzylsulfonyl)amino]-2-oxo-6-propyl-1(2H)-pyridinyl]acetyl]amino)methyl]-6-methyl-2-pyridinylcarbamate | C29H37N5O6S | 详情 | 详情 |