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【结 构 式】 
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【药物名称】SK-1080, KR-31080 【化学名称】2-Butyl-5-methyl-6-(1-oxido-2-pyridinyl)-3-[2′-(1H-tetrazol- 5-yl)biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine 【CA登记号】174800-22-7 【 分 子 式 】C30H28N8O 【 分 子 量 】516.61066 |
【开发单位】Korea Res. Inst. Chem. Technol. (Originator) 【药理作用】PHARMACOLOGICAL TOOLS |
合成路线1
Bromination of 6-aminopicoline (I) in aqueous H2SO4 gave bromopyridine (II), which was subsequently nitrated in cold H2SO4 to afford (III). Reduction of the nitro group of (III) with iron powder and HCl provided diamine (IV). The imidazopyridine system (VI) was then synthesized by condensation of (IV) with valeric acid (V) in polyphosphoric acid at 110 C. Alkylation of (VI) with the biphenylmethyl bromide (VII) in the presence of K2CO3 in DMF gave (VIII), which was coupled in turn with 2-(tri-n-butylstannyl)pyridine (IX) in the presence of Pd(PPh3)4 to produce the 6-(2-pyridinyl)-imidazopyridine derivative (X). Further oxidation of (X) with meta-chloroperbenzoic acid yielded the N-oxide (XI). Finally, deprotection of the tetrazole by treatment with methanolic HCl provided the target compound.
| 【1】 Kim, N.J.; Seo, H.W.; Lee, S.H.; Shin, W.S.; Yi, K.Y.; Yoo, S.E.; Chan, O.J.; Jung, Y.S.; Lee, H.S.; Shin, Y.A.; Lee, B.H.; Kim, H.R.; Kim, S.J.; Suh, J.H. (Korea Research Institute of Chemical Technology); Pyridyl imidazole derivs. and processes for the preparation thereof. WO 9534564 . |
| 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) | 19678 | 6-methyl-2-pyridinamine; 6-methyl-2-pyridinylamine; 6-amino-2-picoline; 2-Amino-6-methylpyridine | 1824-81-3 | C6H8N2 | 详情 | 详情 |
| (II) | 18337 | 5-bromo-6-methyl-2-pyridinamine; 5-bromo-6-methyl-2-pyridinylamine; 6-AMINO-3-BROMO-2-METHYLPYRIDINE | 42753-71-9 | C6H7BrN2 | 详情 | 详情 |
| (III) | 19680 | 5-bromo-6-methyl-3-nitro-2-pyridinamine; 5-bromo-6-methyl-3-nitro-2-pyridinylamine | C6H6BrN3O2 | 详情 | 详情 | |
| (IV) | 19681 | 2-amino-5-bromo-6-methyl-3-pyridinylamine; 5-bromo-6-methyl-2,3-pyridinediamine | C6H8BrN3 | 详情 | 详情 | |
| (V) | 19682 | pentanoic acid | 109-52-4 | C5H10O2 | 详情 | 详情 |
| (VI) | 19683 | 6-bromo-2-butyl-5-methyl-1H-imidazo[4,5-b]pyridine | C11H14BrN3 | 详情 | 详情 | |
| (VII) | 19684 | 1-[5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1H-1,2,3,4-tetraazol-1-yl]ethyl ethyl ether; 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazole | C18H19BrN4O | 详情 | 详情 | |
| (VIII) | 19685 | 6-bromo-2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-3H-imidazo[4,5-b]pyridine; 1-(5-[4'-[(6-bromo-2-butyl-5-methyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1'-biphenyl]-2-yl]-1H-1,2,3,4-tetraazol-1-yl)ethyl ethyl ether | C29H32BrN7O | 详情 | 详情 | |
| (IX) | 19686 | (2-pyridyl)tributyltin;2-(tributylstannyl)pyridine;(2-Pyridinyl)tributylstannane;2-(1,1,1-Tributylstannyl)pyridine;2-(Tri-n-butylstannyl)pyridine;2-(Tributylstannyl)pyridine;2-(Tributyltin)pyridine;2-Pyridyltri-n-butyltin;2-Pyridyltributylstannane;2-Pyridyltributyltin;Tri-n-butyl(2-pyridyl)tin;Tri-n-butyl-2-pyridylstannane;Tributyl(pyridin-2-yl)stannane;Tributyl-2-pyridylstannane;Tributyl-2-pyridyltin | 17997-47-6 | C17H31NSn | 详情 | 详情 |
| (X) | 19687 | 2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-6-(2-pyridinyl)-3H-imidazo[4,5-b]pyridine; 1-[5-(4'-[[2-butyl-5-methyl-6-(2-pyridinyl)-3H-imidazo[4,5-b]pyridin-3-yl]methyl][1,1'-biphenyl]-2-yl)-1H-1,2,3,4-tetraazol-1-yl]ethyl ethyl ether | C34H36N8O | 详情 | 详情 | |
| (XI) | 19688 | 2-[2-butyl-3-([2'-[1-(1-ethoxyethyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-methyl-3H-imidazo[4,5-b]pyridin-6-yl]-1-pyridiniumolate | C34H36N8O2 | 详情 | 详情 |