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【结 构 式】

【分子编号】27214

【品名】tert-butyl 2-[3-amino-2-oxo-6-propyl-1(2H)-pyridinyl]acetate

【CA登记号】

【 分 子 式 】C14H22N2O3

【 分 子 量 】266.34036

【元素组成】C 63.14% H 8.33% N 10.52% O 18.02%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

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
Extended Information