2-bromo-2-[4-(methylsulfonyl)phenyl]-1-phenyl-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】19792

【品名】2-bromo-2-[4-(methylsulfonyl)phenyl]-1-phenyl-1-ethanone

【CA登记号】

【分子式】C₁₅H₁₃BrO₃S

【分子量】353.23642

【元素组成】C 51% H 3.71% Br 22.62% O 13.59% S 9.08%

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：(V)

The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III), which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV). The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1), which is finally cyclocondesed with thiazol-2-amine (VI) in refluxing ethanol or isopentanol.

参考文献中间体

合成目标

【1】 Gauthier, J.Y.; Lau, C.K.; Leblanc, Y.; Li, C.-S.; Roy, P.; Therien, M.; Wang, Z. (Merck Frosst Canada Inc.); Aryl substd. 5,5 fused aromatic nitrogen cpds. as anti-inflammatory agents. EP 0802917; JP 1999501902; US 5552422; WO 9621667 .

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)	19789	bromo[4-(methylsulfanyl)benzyl]magnesium		C₈H₉BrMgS	详情	详情
(II)	19788	N-methoxy-N-methylbenzamide		C₉H₁₁NO₂	详情	详情
(III)	19790	2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone		C₁₅H₁₄OS	详情	详情
(IV)	19791	2-bromo-2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone		C₁₅H₁₃BrOS	详情	详情
(V)	19792	2-bromo-2-[4-(methylsulfonyl)phenyl]-1-phenyl-1-ethanone		C₁₅H₁₃BrO₃S	详情	详情
(VI)	19795	2-Thiazolamine; 1,3-thiazol-2-amine; 1,3-thiazol-2-ylamine	96-50-4	C₃H₄N₂S	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 Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III), which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV). The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1), which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII). Finally, this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.

参考文献中间体

合成目标

【1】 Therien, M.; et al.; Synthesis and biological evaluation of 5, 6-diarylimidazo[2.1-b]thiazole as selective COX-2 inhibitors. Bioorg Med Chem Lett 1997, 7, 1, 47.
【2】 Trimble, L.A.; et al.; Characterization of the in vitro oxidative metabolites of the COX-2 selective inhibitor L-766,112. Bioorg Med Chem Lett 1997, 7, 1, 53.
【3】 Roy, P.; et al.; A new series of selective COX-2 inhibitors: 5, 6-Diarylthiazolo[3,2-b][1,2,4]triazoles. Bioorg Med Chem Lett 1997, 7, 1, 57.
【4】 Gauthier, J.Y.; Lau, C.K.; Leblanc, Y.; Li, C.-S.; Roy, P.; Therien, M.; Wang, Z. (Merck Frosst Canada Inc.); Aryl substd. 5,5 fused aromatic nitrogen cpds. as anti-inflammatory agents. EP 0802917; JP 1999501902; US 5552422; WO 9621667 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	19788	N-methoxy-N-methylbenzamide	C₉H₁₁NO₂	详情	详情
(II)	19789	bromo[4-(methylsulfanyl)benzyl]magnesium	C₈H₉BrMgS	详情	详情
(III)	19790	2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone	C₁₅H₁₄OS	详情	详情
(IV)	19791	2-bromo-2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone	C₁₅H₁₃BrOS	详情	详情
(V)	19792	2-bromo-2-[4-(methylsulfonyl)phenyl]-1-phenyl-1-ethanone	C₁₅H₁₃BrO₃S	详情	详情
(VI)	19793	4H-1,2,4-triazol-3-ylhydrosulfide; 4H-1,2,4-triazole-3-thiol	C₂H₃N₃S	详情	详情
(VII)	19794	2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)-1-ethanone	C₁₇H₁₅N₃O₃S₂	详情	详情

Extended Information