【结 构 式】 |
【分子编号】25959 【品名】3-ethoxy-2-cyclopenten-1-one 【CA登记号】 |
【 分 子 式 】C7H10O2 【 分 子 量 】126.1552 【元素组成】C 66.65% H 7.99% O 25.36% |
合成路线1
该中间体在本合成路线中的序号:(I)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.
【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:(XI)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).
【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 | CAS号 | 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 |