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【结 构 式】

【分子编号】19001

【品名】1-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1-ethanone

【CA登记号】

【 分 子 式 】C15H13FOS

【 分 子 量 】260.3320232

【元素组成】C 69.21% H 5.03% F 7.3% O 6.15% S 12.32%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

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:(V)

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
Extended Information