【结 构 式】 |
【分子编号】26602 【品名】2-hydroxy-6-methylnicotinic acid 【CA登记号】38116-61-9 |
【 分 子 式 】C7H7NO3 【 分 子 量 】153.13752 【元素组成】C 54.9% H 4.61% N 9.15% O 31.34% |
合成路线1
该中间体在本合成路线中的序号:(IX)The intermediate 2-[3-(benzylsulfonamido)-6-methyl-2-oxo-1,2-dihydropyridin-1-yl]acetic acid (VI) has been obtained as follows: The reaction of 2-hydroxy-6-methylpyridine-3-carboxylic acid (IX) with diphenylphosphoryl azide (DPPA), triethylamine and benzyl alcohol in refluxing dioxane gives 3-(benzyloxycarbonylamino)-6-methylpyridin-2(1H)-one (X), which is condensed with tert-butyl bromoacetate (II) by means of NaH in THF yielding the expected condensation product (XI). The deprotection od the amino group of (XI) with H2 over Pd/C in ethanol/water gives the aminopyridone (XII), which is acylated with benzylsulfonylchloride (XIII) in pyridine yielding the sulfonamide (XIV). Finally, the tert-butyl ester group of (XIV) is hydrolyzed with HCl in ethyl acetate to afford the target intermediate (VI).
【1】 Naylor-Olsen, A.M.; Newton, C.L.; Isaacs, R.C.A.; Dorsey, B.D. (Merck & Co., Inc.); Thrombin inhibitors. EP 0969840; US 5932606; WO 9842342 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 26599 | 2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid | C15H16N2O5S | 详情 | 详情 | |
(IX) | 26602 | 2-hydroxy-6-methylnicotinic acid | 38116-61-9 | C7H7NO3 | 详情 | 详情 |
(X) | 26603 | benzyl 6-methyl-2-oxo-1,2-dihydro-3-pyridinylcarbamate | C14H14N2O3 | 详情 | 详情 | |
(XI) | 26604 | tert-butyl 2-[3-[[(benzyloxy)carbonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate | C20H24N2O5 | 详情 | 详情 | |
(XII) | 26605 | tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate | C12H18N2O3 | 详情 | 详情 | |
(XIII) | 25151 | phenylmethanesulfonyl chloride | 1939-99-7 | C7H7ClO2S | 详情 | 详情 |
(XIV) | 26606 | tert-butyl 2-[3-[(benzylsulfonyl)amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetate | C19H24N2O5S | 详情 | 详情 |