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【结 构 式】 
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【药物名称】 【化学名称】N2-[3-Methoxy-4-(5-oxazolyl)phenyl]-6-phenyl-N4-[2-(3-pyridyl)ethyl]-1,3,5-triazine-2,4-diamine 【CA登记号】267646-31-1 【 分 子 式 】C26H23N7O2 【 分 子 量 】465.51891 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】IMMUNOMODULATING AGENTS, Immunosuppressants, Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitors |
合成路线1
Oxidation of 2-methoxy-4-nitrotoluene (I) with CrO3 in the presence of sulfuric acid and acetic anhydride produced acylal (II), which was further hydrolyzed to the benzaldehyde (III) under acidic conditions. The isoxazole derivative (IV) was obtained by treatment of aldehyde (III) with tosylmethyl isocyanide in the presence of K2CO3 in refluxing methanol. Then, catalytic hydrogenation of the nitro group of (IV) over Pd/C afforded aniline (V).
| 【1】 Murali Dhar, T.G.; Pitts, W.J.; Guo, J.; et al.; Rapid synthesis of novel inosine monophosphate dehydrogenase (IMPDH) inhibitors. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 214. |
| 【2】 Liu, C.; Leftheris, K.; Pitts, W.J.; Iwanowicz, E.J.; Dhar, T.G.M.; Gu, H.H. (Bristol-Myers Squibb Co.); Cpds. derived from an amine nucleus that are inhibitors of IMPDH enzyme. EP 1126843; US 6399773; WO 0025780 . |
| 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) | 39654 | methyl 2-methyl-5-nitrophenyl ether; 2-methoxy-1-methyl-4-nitrobenzene | 13120-77-9 | C8H9NO3 | 详情 | 详情 |
| (II) | 39655 | (acetoxy)(2-methoxy-4-nitrophenyl)methyl acetate | C12H13NO7 | 详情 | 详情 | |
| (III) | 39656 | 2-methoxy-4-nitrobenzaldehyde | C8H7NO4 | 详情 | 详情 | |
| (IV) | 39657 | methyl 5-nitro-2-(1,3-oxazol-5-yl)phenyl ether; 5-(2-methoxy-4-nitrophenyl)-1,3-oxazole | C10H8N2O4 | 详情 | 详情 | |
| (V) | 39658 | C10H10N2O2 | 详情 | 详情 |
合成路线2
Addition of phenylmagnesium bromide (VII) to cyanuric chloride (VI) provided 2,4-dichloro-6-phenyltriazine (VIII). This was subsequently condensed with aniline (V) to afford the aminotriazine (IX). Finally, displacement of the remaining chlorine of (IX) with 2-(3-pyridyl)ethylamine (X) furnished the target diaminotriazine derivative.
| 【1】 Murali Dhar, T.G.; Pitts, W.J.; Guo, J.; et al.; Rapid synthesis of novel inosine monophosphate dehydrogenase (IMPDH) inhibitors. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 214. |
| 【2】 Liu, C.; Leftheris, K.; Pitts, W.J.; Iwanowicz, E.J.; Dhar, T.G.M.; Gu, H.H. (Bristol-Myers Squibb Co.); Cpds. derived from an amine nucleus that are inhibitors of IMPDH enzyme. EP 1126843; US 6399773; WO 0025780 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 39658 | C10H10N2O2 | 详情 | 详情 | ||
| (VI) | 23813 | 2,4,6-Trichloro-s-triazine; Cyanuric chloride; Trichlorocyanidine; Tricyanogen chloride; 2,4,6-Trichloro-1,3,5-triazine | 108-77-0 | C3Cl3N3 | 详情 | 详情 |
| (VII) | 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 |
| (VIII) | 53552 | 4,6-Dichloro-2-phenyltriazine | 1700-02-3 | C9H5Cl2N3 | 详情 | 详情 |
| (IX) | 53553 | N-(4-chloro-6-phenyl-1,3,5-triazin-2-yl)-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amine; 4-chloro-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-6-phenyl-1,3,5-triazin-2-amine | n/a | C19H14ClN5O2 | 详情 | 详情 |
| (X) | 53554 | 2-(3-Pyridyl)ethylamine; 3-(2-Aminoethyl)pyridine | 20173-24-4 | C7H10N2 | 详情 | 详情 |