Trimethoxy(3-pyridyl)boranuide lithium salt -Drug Synthesis Database

【结构式】

【分子编号】30006

【品名】Trimethoxy(3-pyridyl)boranuide lithium salt

【CA登记号】

【分子式】C₈H₁₃BLiNO₃

【分子量】188.94816

【元素组成】C 50.85% H 6.93% B 5.72% Li 3.67% N 7.41% O 25.4%

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：(VIII)

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：(VII)

Aldol condensation between 5'-fluoro-2'-hydroxyacetophenone (I) and 4-(methylthio)benzaldehyde (II) produces chalcone (III). Oxidative cyclization of (III) in hot DMSO in the presence of iodine leads to the flavone compound (IV). Further oxidation of the methylthio group of (IV) employing oxone furnishes sulfone (V). Conversion of flavone (V) into the 3-iodo derivative (VI) is carried out by treatment with iodine and bis(trifluoroacetoxy)iodobenzene. Finally, Suzuki coupling of the iodoflavone (VI) with lithium trimethoxy-3-pyridylboronate (VII) provides the desired 2,3-diaryl benzopyranone

参考文献中间体

合成目标

【1】 Joo, Y.H.; Kim, J.K.; Kang, S-H.; Noh, M-S.; Ha, J-Y.; Choi, J.K.; Lim, K.M.; Lee, C.H.; Chung, S.; Diarylbenzopyran derivatives as a selective inhibitor of cyclooxygenase-2. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 313.
【2】 Kim, J.K.; Choi, J.K.; Lee, C.H.; Joo, Y.H.; Noh, M.-S.; Ha, J.-Y.; Lim, K.M.; Kang, S.-H. (Pacific Corp.); Diarylbenzopyran derivs. as cyclooxygenase-2 inhibitors. EP 1105384; JP 2002523410; US 6340694; WO 0010993 .

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)	60391	1-(5-fluoro-2-hydroxyphenyl)-1-ethanone	394-32-1	C₈H₇FO₂	详情	详情
(II)	18815	4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde	3446-89-7	C₈H₈OS	详情	详情
(III)	60392	(E)-1-(5-fluoro-2-hydroxyphenyl)-3-[4-(methylsulfanyl)phenyl]-2-propen-1-one		C₁₆H₁₃FO₂S	详情	详情
(IV)	60393	6-fluoro-2-[4-(methylsulfanyl)phenyl]-4H-chromen-4-one		C₁₆H₁₁FO₂S	详情	详情
(V)	60394	6-fluoro-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one		C₁₆H₁₁FO₄S	详情	详情
(VI)	60395	6-fluoro-3-iodo-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one		C₁₆H₁₀FIO₄S	详情	详情
(VII)	30006	Trimethoxy(3-pyridyl)boranuide lithium salt		C₈H₁₃BLiNO₃	详情	详情

Extended Information