2-fluoro-4-bromobenzyl bromide; 4-bromo-1-(bromomethyl)-2-fluorobenzene -Drug Synthesis Database

【结构式】

【分子编号】22904

【品名】2-fluoro-4-bromobenzyl bromide; 4-bromo-1-(bromomethyl)-2-fluorobenzene

【CA登记号】76283-09-5

【分子式】C₇H₅Br₂F

【分子量】267.9231032

【元素组成】C 31.38% H 1.88% Br 59.65% F 7.09%

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：(II)

The condensation of ethyl 3,4-dihydro-4-oxo-phthalazine-1-acetate (I) with 4-bromo-2-fluoro benzyl bromide (II) by means of NaH in hot DMF gives ethyl 3-(4-bromo-2-fluorobenzyl)-3,4-dihydro-4-oxophthalazine-1-acetate (III), which is saponified with KOH in refluxing ethanol.

参考文献中间体

合成目标

【1】 Pfaffli, P. (Novartis AG); Increasing vigilance or treating cerebral insuffi. GB 1492579; US 4146643 .
【2】 Castaner, J.; Prous, J.; ICI-128436. Drugs Fut 1987, 12, 4, 347.

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)	12095	ethyl 2-(4-oxo-3,4-dihydro-1-phthalazinyl)acetate; Ethyl 3,4-dihydro-4-oxo-1-phthalazineacetate	25947-13-1	C₁₂H₁₂N₂O₃	详情	详情
(II)	22904	2-fluoro-4-bromobenzyl bromide; 4-bromo-1-(bromomethyl)-2-fluorobenzene	76283-09-5	C₇H₅Br₂F	详情	详情
(III)	22905	ethyl 2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4-dihydro-1-phthalazinyl]acetate		C₁₉H₁₆BrFN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromo-2-fluorobenzyl bromide (II) in the presence of n-butyllithium, followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III). Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V), which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI). Finally, Suzuki coupling of (VI) with 5-butyl-2-thiopheneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.

参考文献中间体

合成目标

【1】 McMillan, M.; Cudaback, E.; Misra-Press, A.; et al.; Synthesis and biological studies of a novel inhibitor of NF-kappaB. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 213.
【2】 De Laszlo, S.E.; Chang, L.L.; Kim, D.; Mantlo, N.B. (Merck & Co., Inc.); Substd. pyridyl pyrroles, compsns. containing such cpds. and methods of use. EP 0859771; JP 1999514651; WO 9716442 .
【3】 de Laszlo, S.E.; Kim, D.; Chang, L.L.; Mantlo, N.B. (Merck & Co., Inc.); Substd. pyridyl pyrroles, compsns. containing such cpds. and methods of use. US 5776954 .

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)	29418	4-(dimethoxymethyl)pyridinemethoxy(4-pyridinyl)methyl methyl ether		C₈H₁₁NO₂	详情	详情
(II)	22904	2-fluoro-4-bromobenzyl bromide; 4-bromo-1-(bromomethyl)-2-fluorobenzene	76283-09-5	C₇H₅Br₂F	详情	详情
(III)	29419	2-(4-bromo-2-fluorophenyl)-1-(4-pyridinyl)-1-ethanone		C₁₃H₉BrFNO	详情	详情
(IV)	16720	2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone	536-38-9	C₈H₆BrClO	详情	详情
(V)	29420	2-(4-bromo-2-fluorophenyl)-4-(4-chlorophenyl)-1-(4-pyridinyl)-1,4-butanedione		C₂₁H₁₄BrClFNO₂	详情	详情
(VI)	29421	4-[3-(4-bromo-2-fluorophenyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]pyridine		C₂₁H₁₃BrClFN₂	详情	详情
(VII)	29422	5-butyl-2-thienylboronic acid		C₈H₁₃BO₂S	详情	详情

Extended Information