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【结 构 式】 
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【分子编号】19004 【品名】4-[2-(2-chlorophenyl)-4-(4-fluorophenyl)-1,3-thiazol-5-yl]phenyl methyl sulfide; 2-(2-chlorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfanyl)phenyl]-1,3-thiazole 【CA登记号】 |
【 分 子 式 】C22H15ClFNS2 【 分 子 量 】411.9509432 【元素组成】C 64.14% H 3.67% Cl 8.61% F 4.61% N 3.4% S 15.57% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of 4-(methylsulfanyl)benzaldehyde (I) with 4-fluorophenylacetic acid (II) in refluxing acetic anhydride containing one equivalent of triethylamine, followed by aqueous hydrolysis, provided the diarylpropenoic acid (III). Curtius rearrangement of acid (III) by treatment with diphenylphosphoryl azide in cold toluene, and subsequent hydrolysis of the intermediate isocyanate afforded diarylethanone (IV), which was then brominated in a solution of HBr in acetic acid to give bromoketone (V). The cyclization of this bromoketone with 2-chlorothiobenzamide (VI) in refluxing acetonitrile gave rise to thiazole (VII), and then, oxidation with meta-chloroperbenzoic acid in dichloromethane provided the target sulfone.
| 【1】 Talley, J.J.; Carter, J.S.; Collins, P.W.; Kramer, S.W.; Penning, T.D.; Rogier, D.J. Jr.; Rogers, R.S. (Pharmacia Corp.); Substd. thiazoles for the treatment of inflammation. EP 0772606; JP 1998504542; US 5668161; WO 9603392 . |
| 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) | 18815 | 4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde | 3446-89-7 | C8H8OS | 详情 | 详情 |
| (II) | 18999 | 4-Fluorophenylacetic acid; 2-(4-Fluorophenyl)acetic acid | 405-50-5 | C8H7FO2 | 详情 | 详情 |
| (III) | 19000 | (E)-2-(4-fluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-propenoic acid | C16H13FO2S | 详情 | 详情 | |
| (IV) | 19001 | 1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone | C15H13FOS | 详情 | 详情 | |
| (V) | 19002 | 2-bromo-1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone | C15H12BrFOS | 详情 | 详情 | |
| (VI) | 19003 | 2-chlorobenzenecarbothioamide | 15717-17-6 | C7H6ClNS | 详情 | 详情 |
| (VII) | 19004 | 4-[2-(2-chlorophenyl)-4-(4-fluorophenyl)-1,3-thiazol-5-yl]phenyl methyl sulfide; 2-(2-chlorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfanyl)phenyl]-1,3-thiazole | C22H15ClFNS2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The precursor deoxybenzoin (V) was prepared via Perkin condensation of 4-fluorophenylacetic acid (I) with 4-(methylsulfanyl)benzaldehyde (II) to yield the alpha-phenylcinnamic acid derivative (III), followed by Curtius rearrangement of the corresponding acylazide, and further hydrolysis of the intermediate isocyanate (IV) with HCl in t-BuOH. Alternatively, Friedel-Crafts acylation of fluorobenzene with acid chloride (VI) yielded deoxyenzoin (V). Bromoketone (VII) was then obtained by bromination of (V) in the presence of HBr and AcOH. Subsequent condensation of (VII) with 2-chlorothiobenzamide (VIII) formed thiazole (IX). Finally, the sulfide group of (IX) was oxidized to sulfone using m-chloroperbenzoic acid.
| 【1】 Carter, J.S.; et al.; Design and synthesis of sulfonyl-substituted 4,5-diaylthiazoles as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 8, 1167. |
| 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) | 18999 | 4-Fluorophenylacetic acid; 2-(4-Fluorophenyl)acetic acid | 405-50-5 | C8H7FO2 | 详情 | 详情 |
| (II) | 18815 | 4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde | 3446-89-7 | C8H8OS | 详情 | 详情 |
| (III) | 19000 | (E)-2-(4-fluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-propenoic acid | C16H13FO2S | 详情 | 详情 | |
| (IV) | 25754 | (E)-1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]ethenyl isocyanate; 1-fluoro-4-[(E)-1-isocyanato-2-[4-(methylsulfanyl)phenyl]ethenyl]benzene | C16H12FNOS | 详情 | 详情 | |
| (V) | 19001 | 1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone | C15H13FOS | 详情 | 详情 | |
| (VI) | 25755 | 2-[4-(methylsulfanyl)phenyl]acetyl chloride | C9H9ClOS | 详情 | 详情 | |
| (VII) | 19002 | 2-bromo-1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone | C15H12BrFOS | 详情 | 详情 | |
| (VIII) | 19003 | 2-chlorobenzenecarbothioamide | 15717-17-6 | C7H6ClNS | 详情 | 详情 |
| (IX) | 19004 | 4-[2-(2-chlorophenyl)-4-(4-fluorophenyl)-1,3-thiazol-5-yl]phenyl methyl sulfide; 2-(2-chlorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfanyl)phenyl]-1,3-thiazole | C22H15ClFNS2 | 详情 | 详情 |