(Z)-2,3-dibromo-4-oxo-2-butenoic acid -Drug Synthesis Database

【结构式】

【分子编号】22280

【品名】(Z)-2,3-dibromo-4-oxo-2-butenoic acid

【CA登记号】21577-50-4

【分子式】C₄H₂Br₂O₃

【分子量】257.86608

【元素组成】C 18.63% H 0.78% Br 61.97% O 18.61%

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：(III)

Intermediate 2-benzylpyridazinone (V) was obtained either by alkylation of dibromopyridazinone (I) with benzyl bromide (II) or by condensation of mucobromic acid (III) with benzylhydrazine (IV). Alkaline hydrolysis of (V) with KOH in HMPA then provided the hydroxy derivative (VI). Further treatment of (VI) with trifluoromethanesulfonic anhydride and Et3N produced sulfonate (VII), which was subsequently coupled with 4-(methylthio)phenylboronic acid (VIII) in the presence of palladium catalyst and Na2CO3. Oxidation of the resulting sulfide (IX) with magnesium monoperphthalate (MMPP) in CH2Cl2 gave the corresponding sulfone (X). Finally, the reaction of (X) with isopropanol in the presence of Cs2CO3 furnished the target isopropyl ether.

参考文献中间体

合成目标

【1】 Ojima, I.; Bombardelli, E. (Affymax Technologies, NV; State University of New York, Albany); Anti-tumor cpds., pharmaceutical compsns., methods for preparation thereof and for treatment. US 5705508 .

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)	22278	4,5-dibromo-3(2H)-pyridazinone	5788-58-9	C₄H₂Br₂N₂O	详情	详情
(II)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(III)	22280	(Z)-2,3-dibromo-4-oxo-2-butenoic acid	21577-50-4	C₄H₂Br₂O₃	详情	详情
(IV)	22281	1-benzylhydrazine		C₇H₁₀N₂	详情	详情
(V)	22282	2-benzyl-4,5-dibromo-3(2H)-pyridazinone		C₁₁H₈Br₂N₂O	详情	详情
(VI)	22283	2-benzyl-4-bromo-5-hydroxy-3(2H)-pyridazinone		C₁₁H₉BrN₂O₂	详情	详情
(VII)	22284	1-benzyl-5-bromo-6-oxo-1,6-dihydro-4-pyridazinyl trifluoromethanesulfonate		C₁₂H₈BrF₃N₂O₄S	详情	详情
(VIII)	18561	4-(methylsulfanyl)phenylboronic acid	98546-51-1	C₇H₉BO₂S	详情	详情
(IX)	22286	2-benzyl-4-bromo-5-[4-(methylsulfanyl)phenyl]-3(2H)-pyridazinone		C₁₈H₁₅BrN₂OS	详情	详情
(X)	22287	2-benzyl-4-bromo-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone		C₁₈H₁₅BrN₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Diazotization of 3,4-difluoroaniline (I), followed by reduction with SnCl2 gives rise to hydrazine (II). This is then condensed with mucobromic acid (III) in refluxing AcOH to produce the pyridazinone (IV). Selective displacement of the 4-bromo of (IV) with the sodium alkoxide of 3-methyl-1,3-butanediol (V) yields ether (VI). 4-(Methylsulfanyl)benzeneboronic acid (VIII) is prepared by metalation of 4-bromothioanisole (VII) with butyl lithium, followed by reaction with trimethyl borate, and aqueous work-up. Suzuki coupling of boronic acid (VIII) with bromopyridazinone (VI) furnishes the 5-(methylsufanylphenyl)pyridazinone (IX). Finally, the sulfide group of (IX) is oxidized to the target sulfone by using peracetic acid in cold dichloromethane.

参考文献中间体

合成目标

【1】 Stewart, A.O.; Black, L.A.; Basha, A.; Patel, M.V.; Kolasa, T.; Coghlan, M.J.; Liu, H.; Kort, M.E.; McCarty, C.M.; Rohde, J.J. (Abbott Laboratories Inc.); Prostaglandin endoperoxide H synthase biosynthesis inhibitors. EP 1124804; JP 2003512292; WO 0024719 .

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)	13451	3,4-Difluoroaniline; 3,4-Difluorophenylamine	3863-11-4	C₆H₅F₂N	详情	详情
(II)	61025	1-(3,4-difluorophenyl)hydrazine		C₆H₆F₂N₂	详情	详情
(III)	22280	(Z)-2,3-dibromo-4-oxo-2-butenoic acid	21577-50-4	C₄H₂Br₂O₃	详情	详情
(IV)	61026	4,5-dibromo-2-(3,4-difluorophenyl)-3(2H)-pyridazinone		C₁₀H₄Br₂F₂N₂O	详情	详情
(V)	61027	3-methyl-1,3-butanediol		C₅H₁₂O₂	详情	详情
(VI)	61028	5-bromo-2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-3(2H)-pyridazinone		C₁₅H₁₅BrF₂N₂O₃	详情	详情
(VII)	19266	4-bromophenyl methyl sulfide; 1-bromo-4-(methylsulfanyl)benzene	104-95-0	C₇H₇BrS	详情	详情
(VIII)	18561	4-(methylsulfanyl)phenylboronic acid	98546-51-1	C₇H₉BO₂S	详情	详情
(IX)	61029	2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-[4-(methylsulfanyl)phenyl]-3(2H)-pyridazinone		C₂₂H₂₂F₂N₂O₃S	详情	详情

Extended Information