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at 230℃; for 1 h; Inert atmosphere; Sealed tube; Microwave irradiation
c) 5 -bromo-7-fluoro- 1 -benzofuranA solution of 5-bromo-7-fluoro-l-benzofuran-2-carboxylic acid (1.274 mmol) in quinoline (2 mL) was treated with copper dust (0.236 mmol). The reaction was purged with nitrogen, sealed and irradiated in a microwave reactor at 230 °C for 60 min. The solution was diluted with ethyl acetate and was filtered through Celite. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (hexanes) to provide the title compound as a clear oil (280 mg, 100percent yield). 1H NMR (400 MHz,DMSO-de) δ ppm 8.17 (d, J=2.02 Hz, 1 H) 7.77 (d, J=1.77 Hz, 1 H) 7.55 (dd, J=10.48, 1.64 Hz, 1 H) 7.07 (dd, J=3.16, 2.15 Hz, 1 H).
General procedure: Bromoacetaldehyde dimethyl acetal (1.17 mL, 10.0 mmol) and a catalytic amount of sodium iodide were added to a solution (25 mL) of 2-bromo-4-fluorophenol (0.548 mL, 5.00 mmol) and potassium carbonate (1.38 g, 10.0 mmol) in DMF, and stirred at 80C overnight. The solvent was distilled away under reduced pressure. The residue was diluted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane/ethyl acetate). The resulting compound (1.12 g, 4.01 mmol) was dissolved in chlorobenzene (5 mL), and added at 120C to a solution (5 mL) of a polyphosphoric acid (1.5 g) in chlorobenzene. After the reaction solution was stirred at 120C overnight, the solvent was distilled away under reduced pressure. To the residue, ethyl acetate and water were added. Under ice-cooling, this was poured into a 1 N sodium hydroxide aqueous solution, and stirred. After that, the insoluble material was filtered off, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane) to thus obtain the title compound. Yield: 215 mg (1.00 mmol), percentage yield: 20% 1H NMR (CDCl3, 400MHz) delta 6.80-6.84 (m, 1H), 7.20-7.25 (m, 2H), 7.71-7.74 (m, 1H).
2
[ 2105-94-4 ]
[ 253429-19-5 ]
[ 286836-04-2 ]
Yield
Reaction Conditions
Operation in experiment
Preparation X 5-bromo-7-fluorobenzofuran Beginning with 20.5 gm (108 mMol) 2-fluoro-4-bromophenol, 3.0 gm (13%) of the title compound were prepared essentially by the procedure described in Preparation I. 1H-NMR(CDCl3): delta 7.65 (d, J=2.4 Hz, 1H), 7.50 (d, J=1.5 Hz, 1H). 7.19 (dd, JH=1.5 Hz, JF=8.3 Hz, 1H), 6.76 (m, 1H).
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; at 100℃;Inert atmosphere; Sealed tube;
d) 5- { [(3 S)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -4-[4-(7-fluoro- 1 - benzofuran-5-yl)phenyl]-2,4-dihydro-3H-l,2,4-triazol-3-oneA solution of 5-[(3S)-l-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-l,2,4-triazol-3-one (0.297 mmol) in dioxane (1.5 mL) was treated with 5-bromo-7-fluoro-l-benzofuran (0.297 mmol), dichloro[l,l '-bis(diphenylphosphino)ferrocene]palladium(II)- dichloromethane adduct (17 mg), and 2M aq potassium carbonate (0.89 mmol). The reaction mixture was purged with nitrogen, sealed, and stirred at 100 C overnight. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH ~4 using IN aq HC1 and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (20-50% acetonitrile/water + 0.1% NH4OH) to afford the title compound as a beige solid (47%). MS(ES)+ m/e 447.1 [M+H]+.
copper; at 230℃; for 1.0h;Inert atmosphere; Sealed tube; Microwave irradiation;
c) 5 -bromo-7-fluoro- 1 -benzofuranA solution of 5-bromo-7-fluoro-l-benzofuran-2-carboxylic acid (1.274 mmol) in quinoline (2 mL) was treated with copper dust (0.236 mmol). The reaction was purged with nitrogen, sealed and irradiated in a microwave reactor at 230 C for 60 min. The solution was diluted with ethyl acetate and was filtered through Celite. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (hexanes) to provide the title compound as a clear oil (280 mg, 100% yield). 1H NMR (400 MHz,DMSO-de) delta ppm 8.17 (d, J=2.02 Hz, 1 H) 7.77 (d, J=1.77 Hz, 1 H) 7.55 (dd, J=10.48, 1.64 Hz, 1 H) 7.07 (dd, J=3.16, 2.15 Hz, 1 H).
7-fluoro-5-(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71.6%
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In methanol; toluene; at 120℃; for 3.0h;Inert atmosphere;
Compound 28 (<strong>[286836-04-2]5-bromo-7-fluorobenzofuran</strong>, was added to the reaction vessel.5.0 g, 23.2 mmol), compound 13 (4,4,5,5-tetramethyl-2-(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)-1,3, 2-dioxaborolan,6.4 g, 21.0 mmol), toluene (64.0 mL, 10 mL/g),Methanol (6.4 mL, 1 mL/g).After adding Cs2CO3 (13.7 g, 42.0 mmol),Pd(PPh3)4 (1.2 g, 1.1 mmol) was added under a nitrogen atmosphere.The reaction was carried out by refluxing at 120 C for 3 hours.After the reaction, the reaction is cooled to normal temperature.And filtered with celite using ethyl acetate.The filtered solution is washed with brine.It was then dried over anhydrous sodium sulfate and filtered and evaporated.The concentrate was subjected to silica gel column chromatography (hexane:EtOAc = 7:1)Purification to give a white solid compound 29(5.2 g, yield 71.6%).
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