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A solution of 4,5-difluorobenzene-1 ,2-diamine (1.5 g, 10 mmol) in formic acid (20 mL) was heated at 80C for 12 hours. The reaction mixture was cooled to 25C and concentrated under reduced pressure. The residue was recrystallized form Petroleum ether:EtOAc (15: 1 ) to afford 5,6-difluoro- 1 H-benzo[d]imidazole as a yellow solid (1.4 g, 88%). MS (ESI) m/z: 155 [M+H]+.
75%
With orthoformic acid triethyl ester; at 100℃; for 1h;
Step 2: A stirred mixture of 4,5-difluorobenzene-1,2-diamine (1.40 g, 9.7 mmol) from the previous step, formicacid (2.0 mL), and triethyl orthoformate (20 mL) was heated at 100 C for 1 h. The reaction mixture was cooled to rt andconcentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 5%MeOH in DCM to afford 5,6-difluoro-1H-benzo[d]imidazole as (1.12 g, 75%) as a white solid. 1H NMR (300 MHz, CDCl3) delta 8.07 (s, 1H), 7.44 (m, 2H); LCMS (ESI) m/z 155 (M + H)+.
Example 4: Synthesis of 5,6-Difluoro-lH-benzo[d]imidazole EPO <DP n="31"/>EtOCH=C(CN)2 iPrOH [0088] A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 niL of THF was treated with a solution comprised of 6 g OfNa2S2O4 and 3 g NaHCO3 in 30 niL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-l,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6-difluoro-lH-benzo[d]imidazole (8).
In isopropyl alcohol; for 16h;Heating / reflux;
Example 4 Synthesis of 5,6-Difluoro-1H-benzo[d]imidazole A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 mL of THF was treated with a solution comprised of 6 g of Na2S2O4 and 3 g NaHCO3 in 30 mL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-1,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6-difluoro-1H-benzo[d]imidazole (8).
In isopropyl alcohol; for 16h;Heating / reflux;
A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 mL of THF was treated with a solution comprised of 6 g OfNa2SaO4 and 3 g NaHCC>3 in 30 mL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of <n="29"/>ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-l,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6- difluoro-lH-benzo[d]imidazole (8).
General procedure: A mixture of 1a (1b-1n, 0.4 mmol) and PhSiH3 (98 mL, 1.6 mmol)in N,N-dimethylformamide 2a (2b-2c, 1 mL) was stirred at 120 C for 12 h. When the reaction was completed, the resulting mixture was extracted with ethyl acetate three times. The combined organic layer was washed by NaCl aqueous solution and dried over anhydrous Na2SO4, after which the solvent was removed under reduced pressure. The residue was purified by column chromatography onsilica gel with petroleum ether and ethyl acetate (6:1-1:2) to give the corresponding product 3a (3b-3p).
3-bromo-9,10-difluoro-5-methylbenzo[4,5]imidazo[1,2-c]quinazolin-6(5H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With tert.-butylhydroperoxide; In dimethyl sulfoxide; at 90℃; for 0.5h;
N-methyl indole (0.5 mmol), DMSO (5 ml) were added into reaction tube and stirred at 90 C. Then the I2 (0.6 mmol) and TBHP (2.5 mmol) were added into the reaction tube. After 24 h the o-benzenediamine (0.34 mmol) was added into the mixture. The reaction was stopped until the o-benzenediamine was completely consumed as monitored by TLC analysis. After the completion of reaction, 5% Na2S2O3 solution (30 mL) was added to the mixture. The mixture was extracted with EtOAc (3 * 20 ml) and the organic layer was dried by Na2SO4. Then the crude product was purified by silica gel chromatography (petroleum ether/ethyl acetate/dichloromethane 3/1/1).
9-(4-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)phenyl)-9H-carbazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With sodium dithionite; In N,N-dimethyl-formamide; at 140℃; for 24h;Schlenk technique; Inert atmosphere;
Add 4,5-difluoro-o-phenylenediamine (290mg, 2mmol), <strong>[110677-45-7]4-(9H-carbazol-9-yl)benzaldehyde</strong> (540mg, 2mmol), Na2S2O4 (1050mg, 6mmol) into a 50ml Schleck tube, Add 6mL DMF and heat to reflux for 24 hours under nitrogen protection. Dilute the cooled reaction solution with 20mL saturated sodium chloride solution, extract with 3*25mL ethyl acetate, combine the organic phases, add anhydrous MgSO4 to dry, filter to remove anhydrous magnesium sulfate, evaporate the solvent under reduced pressure, petroleum ether: the target product separated by ethyl acetate (6:1) column chromatography, with a yield of 83%.
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