|
【结 构 式】 
|
【药物名称】CJ-13610 【化学名称】4-[3-Fluoro-5-[4-(2-methyl-1H-imidazol-1-yl)phenylsulfanyl]phenyl]tetrahydro-2H-pyran-4-carboxamide hydrochloride 【CA登记号】179420-35-0 【 分 子 式 】C22H23ClFN3O2S 【 分 子 量 】447.96291 |
【开发单位】Pfizer (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, 5-Lipoxygenase Inhibitors |
合成路线1
Alkylation of 3,5-difluorophenylacetonitrile (I) with bis-(2-chloroethyl)ether (II) affords the tetrahydropyran derivative (III). Subsequent displacement of one fluoride group of (III) with sodium methylsulfide in hot DMF yields thioether (IV). Oxidation of (IV) employing NaIO4 leads to sulfoxide (V). Then, Pummerer rearrangement of sulfoxide (V) with trifluoroacetic anhydride, followed by basic hydrolysis, furnishes thiol (VI)
| 【1】 Stevens, R.W.; Mano, T.; Nakao, K.; Okumura, Y. (Pfizer Inc.); 5-Lipoxygenase inhibitors. EP 0787127; JP 1999507322; US 5883106; WO 9611911 . |
| 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) | 60256 | 2-(3,5-difluorophenyl)acetonitrile | C8H5F2N | 详情 | 详情 | |
| (II) | 12060 | Bis(2-chloroethyl) ether; 1-Chloro-2-(2-chloroethoxy)ethane; 2,2'-Dichlorodiethyl ether | 111-44-4 | C4H8Cl2O | 详情 | 详情 |
| (III) | 60257 | 4-(3,5-difluorophenyl)tetrahydro-2H-pyran-4-carbonitrile | C12H11F2NO | 详情 | 详情 | |
| (IV) | 60258 | 4-[3-fluoro-5-(methylsulfanyl)phenyl]tetrahydro-2H-pyran-4-carbonitrile | C13H14FNOS | 详情 | 详情 | |
| (V) | 60259 | 4-[3-fluoro-5-(methylsulfinyl)phenyl]tetrahydro-2H-pyran-4-carbonitrile | C13H14FNO2S | 详情 | 详情 | |
| (VI) | 60260 | 4-(3-fluoro-5-sulfanylphenyl)tetrahydro-2H-pyran-4-carbonitrile | C12H12FNOS | 详情 | 详情 |
合成路线2
Arylation of 2-methylimidazole (VII) with1-fluoro-4-iodobenzene (VIII) gives the iodophenyl imidazole (IX). Then, condensation of aryl iodide (IX) with thiophenol (VI) produces the diaryl sulfide (X). Finally, partial hydrolysis of the cyano group of (X) employing KOH in t-butanol yields the target carboxamide
| 【1】 Stevens, R.W.; Mano, T.; Nakao, K.; Okumura, Y. (Pfizer Inc.); 5-Lipoxygenase inhibitors. EP 0787127; JP 1999507322; US 5883106; WO 9611911 . |
| 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) | 60260 | 4-(3-fluoro-5-sulfanylphenyl)tetrahydro-2H-pyran-4-carbonitrile | C12H12FNOS | 详情 | 详情 | |
| (VII) | 15670 | 2-Methylimidazole; 2-Methyl-1H-imidazole | 693-98-1 | C4H6N2 | 详情 | 详情 |
| (VIII) | 54686 | 1-Fluoro-4-iodobenzene; 4-Fluoroiodobenzene; 4-Iodofluorobenzene; p-Fluoroiodobenzene | 352-34-1 | C6H4FI | 详情 | 详情 |
| (IX) | 60261 | 1-(4-iodophenyl)-2-methyl-1H-imidazole | C10H9IN2 | 详情 | 详情 | |
| (X) | 60262 | 4-(3-fluoro-5-{[4-(2-methyl-1H-imidazol-1-yl)phenyl]sulfanyl}phenyl)tetrahydro-2H-pyran-4-carbonitrile | C22H20FN3OS | 详情 | 详情 |