2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one -Drug Synthesis Database

【结构式】

【分子编号】25957

【品名】2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one

【CA登记号】

【分子式】C₁₂H₁₁BrOS

【分子量】283.18874

【元素组成】C 50.9% H 3.92% Br 28.22% O 5.65% S 11.32%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

The bromination of 3-ethoxy-2-cyclopenten-1-one (I) with Br2 and triethylamine in chloroform gives the 2-bromo derivative (II), which is condensed with 4-bromothioanisole (III) by means of BuLi in THF yielding 2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one (IV). The oxidation of (IV) with Na2WO4 and H2O2 affords the corresponding sulfone (V), which is finally condensed with lithium diisopropyl 3-pyridylboronate (VII) or the corresponding dimethyl ester (VIII) by means of tris(dibenzylideneacetone)dipalladium (III) (Pd2(dba)3) and triphenylphosphine in toluene/propanol/water. The lithium boronates (VII) and (VIII) have been obtained by reaction of 3-bromopyridine (VI) with triisopropyl borate or trimethyl borate and BuLi in ethyl ether.

参考文献中间体

合成目标

【1】 Chan, C.-C.; Brideau, C.; Black, W.C.; et al.; 2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors. J Med Chem 1999, 42, 7, 1274.
【2】 Black, C.; Hughes, G.; Wang, Z. (Merck Frosst Canada Inc.); Pyridinyl-2-cyclopenten-1-ones as selective cyclooxygenase-2 inhibitors. EP 0900201; JP 2000509032; US 5922742; WO 9740012 .

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)	25959	3-ethoxy-2-cyclopenten-1-one		C₇H₁₀O₂	详情	详情
(II)	25960	2-bromo-3-ethoxy-2-cyclopenten-1-one		C₇H₉BrO₂	详情	详情
(III)	19266	4-bromophenyl methyl sulfide; 1-bromo-4-(methylsulfanyl)benzene	104-95-0	C₇H₇BrS	详情	详情
(IV)	25957	2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one		C₁₂H₁₁BrOS	详情	详情
(V)	25958	2-bromo-3-[4-(methylsulfonyl)phenyl]-2-cyclopenten-1-one		C₁₂H₁₁BrO₃S	详情	详情
(VI)	13265	3-Bromopyridine	626-55-1	C₅H₄BrN	详情	详情
(VII)	30005	Triisopropoxy(3-pyridyl)boranuide lithium salt		C₁₄H₂₅BLiNO₃	详情	详情
(VIII)	30006	Trimethoxy(3-pyridyl)boranuide lithium salt		C₈H₁₃BLiNO₃	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 condensation of 2-bromo-2-cyclopentenone (II) with the aryl lithium compound (V) gives the tertiary alcohol (VIII), which is submitted to an oxidation with PDC with simultaneous allylic transposition to provide 2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one (IX). The oxidation of (IX) with H2O2 (Na2WO4) or MCPBA yields the corresponding sulfone (X), which is finally condensed with boronic acid (III) by means of a Pd catalyst as before. The synthetic approaches can also be performed with the arylmagnesium analogue of lithium derivative (V).

参考文献中间体

合成目标

【1】 Black, C. (Merck Frosst Canada Inc.); 2-(3,5-Difluorophenyl)-3-(4-(methyl-sulfonyl)phenyl)-2-cyclopenten-1-one useful as an inhibitor of cyclooxygenase-2. EP 0863134; JP 1998251220 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	25951	2-bromo-2-cyclopenten-1-one		C₅H₅BrO	详情	详情
(III)	25952	3,5-difluorophenylboronic acid	156545-07-2	C₆H₅BF₂O₂	详情	详情
(V)	18808	[4-(methylsulfanyl)phenyl]lithium		C₇H₇LiS	详情	详情
(VIII)	25956	2-bromo-1-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-ol		C₁₂H₁₃BrOS	详情	详情
(IX)	25957	2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one		C₁₂H₁₁BrOS	详情	详情
(X)	25958	2-bromo-3-[4-(methylsulfonyl)phenyl]-2-cyclopenten-1-one		C₁₂H₁₁BrO₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IX)

The bromination of 3-ethoxy-2-cyclopentenone (XI) gives the 2-bromo derivative (XII), which is condensed with the aryl lithium (V) as before yielding the tertiary alcohol (XIII). Then (XIII) was submitted to an acid rearrangement to provide 2-bromo-3-[4-(sulfanylmethyl)phenyl]-2-cyclopentenone (IX), already obtained in the preceding approaches. The synthetic approaches can also be performed with the arylmagnesium analogue of lithium derivative (V).

参考文献中间体

合成目标

【1】 Chan, C.-C.; Brideau, C.; Black, W.C.; et al.; 2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors. J Med Chem 1999, 42, 7, 1274.
【2】 Black, C. (Merck Frosst Canada Inc.); 2-(3,5-Difluorophenyl)-3-(4-(methyl-sulfonyl)phenyl)-2-cyclopenten-1-one useful as an inhibitor of cyclooxygenase-2. EP 0863134; JP 1998251220 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	18808	[4-(methylsulfanyl)phenyl]lithium	C₇H₇LiS	详情	详情
(IX)	25957	2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one	C₁₂H₁₁BrOS	详情	详情
(XI)	25959	3-ethoxy-2-cyclopenten-1-one	C₇H₁₀O₂	详情	详情
(XII)	25960	2-bromo-3-ethoxy-2-cyclopenten-1-one	C₇H₉BrO₂	详情	详情
(XIII)	25961	2-bromo-3-ethoxy-1-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-ol	C₁₄H₁₇BrO₂S	详情	详情

Extended Information