(E)-2-(4-fluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-propenoic acid -Drug Synthesis Database

【结构式】

【分子编号】19000

【品名】(E)-2-(4-fluorophenyl)-3-[4-(methylsulfanyl)phenyl]-2-propenoic acid

【CA登记号】

【分子式】C₁₆H₁₃FO₂S

【分子量】288.3424232

【元素组成】C 66.65% H 4.54% F 6.59% O 11.1% S 11.12%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【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：(III)

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.

参考文献中间体

合成目标

【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