-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】3-[3-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenoxymethyl]-1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazole

【CA登记号】

【分子式】C₂₉H₂₉FN₂O₅S

【分子量】536.62728

【开发单位】Innothera (Originator)

【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, 5-Lipoxygenase Inhibitors, Cyclooxygenase-2 Inhibitors

合成路线1 合成路线2

合成路线1

Claisen condensation of acetophenone (I) with diethyl oxalate affords the dioxo ester (II). This is condensed with 4-(methylsulfonyl)phenylhydrazine (III) to form the diaryl pyrazole (IV). Ester group reduction in (IV) by means of LiAlH4 provides alcohol (V), which is converted to the corresponding mesylate (VI) upon treatment with methanesulfonyl chloride and Et3N

参考文献中间体

【1】 Barbey, S.; et al.; Synthesis and activity of a new methoxytetrahydropyran derivative as dual cyclooxygenase-2/5-lipoxygenase inhibitor. Bioorg Med Chem Lett 2002, 12, 5, 779.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	45337		C₈H₈O	详情	详情
(II)	60602	ethyl 2,4-dioxo-4-phenylbutanoate	C₁₂H₁₂O₄	详情	详情
(III)	60603	1-[4-(methylsulfonyl)phenyl]hydrazine; 4-hydrazinophenyl methyl sulfone	C₇H₁₀N₂O₂S	详情	详情
(IV)	60604	ethyl 1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-carboxylate	C₁₉H₁₈N₂O₄S	详情	详情
(V)	60605	{1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazol-3-yl}methanol	C₁₇H₁₆N₂O₃S	详情	详情
(VI)	60606	{1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazol-3-yl}methyl methanesulfonate	C₁₈H₁₈N₂O₅S₂	详情	详情

合成路线2

Displacement of 3,5-difluorobromobenzene (VII) with the sodium alkoxide of benzyl alcohol yields the benzyl ether (VIII). Metalation of (VIII) with butyllithium, followed by addition to tetrahydropyran-4-one (IX) furnishes the carbinol adduct (X). This is converted to the methyl ether (XI) by alkylation with iodomethane in the presence of NaH. Then, hydrogenolysis of the O-benzyl group of (XI) over Pd(OH)2 provides phenol (XII). Finally, condensation between phenol (XII) and mesylate (VI) gives rise to the title compound

参考文献中间体

【1】 Barbey, S.; et al.; Synthesis and activity of a new methoxytetrahydropyran derivative as dual cyclooxygenase-2/5-lipoxygenase inhibitor. Bioorg Med Chem Lett 2002, 12, 5, 779.

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)	60606	{1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazol-3-yl}methyl methanesulfonate		C₁₈H₁₈N₂O₅S₂	详情	详情
(VII)	30794	1-bromo-3,5-difluorobenzene	461-96-1	C₆H₃BrF₂	详情	详情
(VIII)	60607	1-(benzyloxy)-3-bromo-5-fluorobenzene; benzyl 3-bromo-5-fluorophenyl ether		C₁₃H₁₀BrFO	详情	详情
(IX)	31563	tetrahydro-4H-pyran-4-one	29943-42-8	C₅H₈O₂	详情	详情
(X)	60608	4-[3-(benzyloxy)-5-fluorophenyl]tetrahydro-2H-pyran-4-ol		C₁₈H₁₉FO₃	详情	详情
(XI)	60609	4-[3-(benzyloxy)-5-fluorophenyl]-4-methoxytetrahydro-2H-pyran; benzyl 3-fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenyl ether		C₁₉H₂₁FO₃	详情	详情
(XII)	60610	3-fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenol		C₁₂H₁₅FO₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)