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【结 构 式】 
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【药物名称】 【化学名称】1-[2-(4-Benzylphenoxy)ethyl]-1H-imidazo[4,5-c]pyridine-4-carbonitrile 【CA登记号】 【 分 子 式 】C22H18N4O 【 分 子 量 】354.41496 |
【开发单位】Pfizer (Originator) 【药理作用】Antiarthritic Drugs, Antipsoriatics, Asthma Therapy, DERMATOLOGIC DRUGS, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, RESPIRATORY DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Leukotriene A4 Hydrolase Inhibitors |
合成路线1
Alkylation of 4-hydroxydiphenylmethane (I) with tert-butyl bromoacetate (II) in the presence of NaH and Bu4NI in DMF affords ether (III). The ester function of (III) is then reduced by LiAlH4 to furnish the primary alcohol (IV), which is subsequently activated as the corresponding tosylate (V) (1,2). Condensation of tosylate (V) with 5-azabenzimidazole (VI) gives rise to a mixture of the three possible regioisomers (VII), (VIII) and (IX), which can be separated by means of flash chromatography. The desired isomer (IX) is then converted to the N-oxide (X) employing m-chloroperbenzoic acid in CHCl3 (1-3). Finally, reaction of N-oxide (X) with cyanotrimethylsilane produces the target nitrile (3).
| 【1】 Synthesis of imidazopyridines and purines as potent inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem Lett 2003, 13, 6, 1137. |
| 【2】 Chandrakumar, N.S.; Chen, B.B.; Clare, M.; Desai, B.N.; Djuric, S.W.; Docter, S.H.; Gasiecki, A.; Haack, R.A.; Liang, C.-D.; Miyashiro, J.M.; Penning, T.D.; Russell, M.A.; Yu, S.S. (Pfizer Inc.); LTA4 hydrolase inhibitors. EP 0804427; EP 1221441; JP 1998512848; WO 9611192 . |
| 【3】 Chandrakumar, N.S.; Chen, B.B.; Clare, M.; Desai, B.N.; Djuric, S.W.; Docter, S.H.; Gasiecki, A.F.; Haack, R.A.; Liang, C.-D.; Miyashiro, J.M.; Penning, T.D.; Russell, M.A.; Yu, S.S. (Pfizer Inc.); LTA4 hydrolase inhibitor pharmaceutical compsns. and methods of use. JP 1998512542; WO 9610999 . |
| 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) | 50817 | 4-Hydroxydiphenylmethane; 4-Benzylphenol; alpha-Phenyl-p-cresol; p-Benzylphenol | 101-53-1 | C13H12O | 详情 | 详情 |
| (II) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (III) | 64434 | tert-butyl 2-(4-benzylphenoxy)acetate | C19H22O3 | 详情 | 详情 | |
| (IV) | 64435 | 2-(4-benzylphenoxy)-1-ethanol | C15H16O2 | 详情 | 详情 | |
| (V) | 64436 | 2-(4-benzylphenoxy)ethyl 4-methylbenzenesulfonate | C22H22O4S | 详情 | 详情 | |
| (VI) | 64437 | 1H-imidazo[4,5-c]pyridine | C6H5N3 | 详情 | 详情 | |
| (VII) | 64438 | 4-benzylphenyl 2-(5H-imidazo[4,5-c]pyridin-5-yl)ethyl ether; 5-[2-(4-benzylphenoxy)ethyl]-5H-imidazo[4,5-c]pyridine | C21H19N3O | 详情 | 详情 | |
| (VIII) | 64439 | 4-benzylphenyl 2-(3H-imidazo[4,5-c]pyridin-3-yl)ethyl ether; 3-[2-(4-benzylphenoxy)ethyl]-3H-imidazo[4,5-c]pyridine | C21H19N3O | 详情 | 详情 | |
| (IX) | 64440 | 1-[2-(4-benzylphenoxy)ethyl]-1H-imidazo[4,5-c]pyridine; 4-benzylphenyl 2-(1H-imidazo[4,5-c]pyridin-1-yl)ethyl ether | C21H19N3O | 详情 | 详情 | |
| (X) | 64441 | 1-[2-(4-benzylphenoxy)ethyl]-1H-imidazo[4,5-c]pyridin-5-ium-5-olate | C21H19N3O2 | 详情 | 详情 |