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【结 构 式】 
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【分子编号】62739 【品名】methyl 2-{4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl}-5-methyl-1,3-dioxane-5-carboxylate 【CA登记号】 |
【 分 子 式 】C21H21FN4O4S 【 分 子 量 】444.4867032 【元素组成】C 56.75% H 4.76% F 4.27% N 12.6% O 14.4% S 7.21% |
合成路线1
该中间体在本合成路线中的序号：(IX)Alkylation of 2-mercapto-4-methylpyrimidine (I) with iodomethane and NaOH affords 2-methylthio-4-methylpyrimidine (II). Condensation of (II) with methyl 4-fluorobenzoate (III) in the presence of sodium hexamethyldisilazide produces ketone (IV), which is further oxidized to dione (V) with DMSO/HBr. Ring closure of dione (V) with glyoxal dimethyl acetal (VI) in the presence of ammonium acetate leads to imidazole (VII). Acid-catalyzed transketalization of (VII) with the dihydroxy ester (VIII) yields the 1,3-dioxane derivative (IX) as a 3:2 mixture of cis- and trans- isomers. After chromatographic separation of the desired trans- isomer, oxidation of the methylthio group with mCPBA furnishes sulfone (X)
| 【1】 McKenna, J.M.; Halley, F.; Souness, J.E.; McLay, I.M.; Pickett, S.D.; Collis, A.J.; Page, K.; Ahmed, I.; An algorithm-directed two-component library synthesized via solid-phase methodology yielding potent and orally bioavailable p38 MAP kinase inhibitors. J Med Chem 2002, 45, 11, 2173. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 49196 | 4-methyl-2-pyrimidinylhydrosulfide; 4-methyl-2-pyrimidinethiol | C5H6N2S | 详情 | 详情 | |
| (II) | 49197 | 4-methyl-2-(methylsulfanyl)pyrimidine; methyl 4-methyl-2-pyrimidinyl sulfide | C6H8N2S | 详情 | 详情 | |
| (III) | 62737 | methyl 4-fluorobenzoate | C8H7FO2 | 详情 | 详情 | |
| (IV) | 49198 | 1-(4-fluorophenyl)-2-[2-(methylsulfanyl)-4-pyrimidinyl]-1-ethanone | C13H11FN2OS | 详情 | 详情 | |
| (V) | 49199 | 1-(4-fluorophenyl)-2-[2-(methylsulfanyl)-4-pyrimidinyl]-1,2-ethanedione | C13H9FN2O2S | 详情 | 详情 | |
| (VI) | 49200 | 2,2-dimethoxyacetaldehyde | C4H8O3 | 详情 | 详情 | |
| (VII) | 62738 | 4-[2-(dimethoxymethyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-(methylsulfanyl)pyrimidine; {4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl}(methoxy)methyl methyl ether | C17H17FN4O2S | 详情 | 详情 | |
| (VIII) | 33803 | methyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate | C6H12O4 | 详情 | 详情 | |
| (IX) | 62739 | methyl 2-{4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl}-5-methyl-1,3-dioxane-5-carboxylate | C21H21FN4O4S | 详情 | 详情 | |
| (X) | 62740 | methyl 2-{4-(4-fluorophenyl)-5-[2-(methylsulfonyl)-4-pyrimidinyl]-1H-imidazol-2-yl}-5-methyl-1,3-dioxane-5-carboxylate | C21H21FN4O6S | 详情 | 详情 |