* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 12 h;
Fourth Step: Synthesis of Intermediate Product (D) (0133) 29.7 g (80.9 mmol) of the intermediate product (C) and 1.4 g (8.1 mmol) of p-toluenesulfonic acid were suspended in 300 mL of xylene and agitated at 150° C. for 12 hours. After cooling, xylene was removed under the reduced pressure to provide a solid, and the solid was recrystallized with methanol to provide 22.4 g (yield: 79percent) of the intermediate product (D).
52%
With toluene-4-sulfonic acid In xylene for 3 h; Heating / reflux
2.1 g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl] benzamide were suspended into 30 mL of xylene, 0.6 g (2.9 mmol) of p-toluenesulfonic acid monohydrate was added, and the whole was refluxed under heating for 3 hours. After the resultant had been stood to cool, the reaction solution was added with ethyl acetate, dichloromethane, and water for filtering insoluble matter out. An organic layer was extracted from a mother liquor, washed with water and a saturated sodium chloride solution, and dried with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by means of silica gel column chromatography to obtain 1.0 g of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole (52percent yield).
52%
With toluene-4-sulfonic acid In xylene for 3 h; Heating / reflux
(3) Synthesis of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole Suspending 2.1 g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl] benzamide obtained in the above step (2) into 30 milliliter of xylene, and adding 0.6 g (2.9 mmol) of p-toluenesulfonic acid 1 hydrate, the resultant solution was azeotropically dehydrated while refluxing with heating for 3 hours. After naturally cooling the reacted solution, ethyl acetate, dichloromethane and water were added to the reacted solution, followed by separating an insoluble substance by filtration. Extracting an organic layer from mother liquor, the organic layer was washed with water and a saturated solution of sodium chloride and then, dried with anhydrous sodium sulfate, followed by removing the solvent by distillation under reduced pressure. Refining the residue with silicagel column chromatography, 1.0 g of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole was obtained as white crystals with a slight pink color (yield: 52 percent).
52%
for 3 h; Reflux
(C-3) Synthesis of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole 2.1g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl]benzamide was suspended in 30 mL of xylene. To the resulting suspension, 0.6g (2.9 mmol) of p-toluenesulfonic acid monohydrate was added, and the resultant was subjected to azeotropic dehydration while heating under reflux for 3 hours. After allowing it to be cool, ethyl acetate, methylene chloride and water were added to the reaction solution, and unsoluble matters were filtered off. An organic phase was extracted from a mother solution, washed with water and saturated saline, and dried with anhydrous sodium sulfate. The solvent was distilled off under a reduced pressure. Residues were purified by silica gel column chromatography, whereby 1.0g of slightly pinky white crystals of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole were obtained (yield 52percent).
30 g
at 250℃; for 3 h;
As shown in synthetic route 4 below, 30 g of intermediate compound M5 was synthesized by a method described in a non-patent document: Chemistry of Materials, 2009, 21(12), 2452.
Stage #1: at 20 - 60℃; for 4 h; Stage #2: at 130 - 250℃; for 3 h; Inert atmosphere
Synthesis of Intermediate 5-C: To a 500ml three-necked round flask with magnetic stirrer was sequentially added with Intermediate 5-B (15.8g, 0.06mol), benzoyl chloride (11.2g, 0.08mol), N-methylpyrrolidone 200ml. After the reaction was stirred at room temperature for 2h, it is continued to warm to 50-60C and was stirred for 2h. After the reaction solution was poured into 200ml of water, the precipitated solid was filtered. After drying under an argon atmosphere and heated to 130C, water is generated, and the reaction at 250C for 3 hours. Cooled to room temperature, extracted with CH2Cl2 to obtain a crude product. The crude product was purified by column chromatography on silica gel, ethyl acetate / petroleum ether as eluent to give 11.7g pale yellow solid, yield 55.9percent.
for 12 h; Inert atmosphere; Schlenk technique; Reflux
A mixture of benzaldehyde (2.02 g, 19.0 mmol) and N-phenylbenzene-1,2-diamine (1.0 g, 5.43 mmol) was dissolved in 2-methoxyethanol (10 mL). Then the mixture was heat to reflux for 12 h. The solvent was removed and the residue was extracted with dichloromethane (30 mL x 3). The organic layer was washed with water, brine and then dried with anhydrous MgSO4, filtered. After filtration, the filtrate was pumped dry in vacuo. The crude residue was subjected to silica gel column chromatography by eluting with hexanes: dichloromethane (1:1) as an eluting to give a brown solid (yield: 43percent).1H NMR (400 MHz, acetone-d6,):δ (ppm) 7.88 (d, J = 8.8 Hz, 3 H), 7.62-7.60 (m, 2 H), 7.42-7.38 (m, 5H), and 7.38-7.25 (m, 3 H); Mass (FAB): m/z: 351.0 [M+H]+.
Reference：
[1] Journal of Materials Chemistry, 2011, vol. 21, # 48, p. 19249 - 19256
[2] Tetrahedron, 2014, vol. 70, # 18, p. 2992 - 2998
[3] Green Chemistry, 2013, vol. 15, # 3, p. 798 - 810
[4] Dalton Transactions, 2013, vol. 42, # 31, p. 11056 - 11065
Reference：
[1] Journal of Materials Chemistry C, 2015, vol. 3, # 21, p. 5430 - 5439
9
[ 100953-52-4 ]
[ 760212-58-6 ]
Reference：
[1] Patent: US9548460, 2017, B2,
10
[ 760212-58-6 ]
[ 5419-55-6 ]
[ 867044-33-5 ]
Yield
Reaction Conditions
Operation in experiment
76.8%
With n-butyllithium In tetrahydrofuran at -78℃;
Synthesis of Intermediate 5-D: In a 250ml three-necked round flask, added was Intermediate 5-C(11.5g, 0.03mol), and 120ml dried THF that underwent treatment with Na /Benzophenone. Liquid nitrogen was used to cool reaction to -78C. While stirring, slowly added dropwise 14.5ml of n-butyllithium (0.036mol, 2.5mol·L-1), and Triisopropyl borate 9.96ml (8.12g, 0.043mol). After the addition was completed, stirred to room temperature. Adding an appropriate amount of dilute hydrochloric acid, hydrolysis, extraction with ethyl acetate, the combined organic phases. The organic solvent was removed by rotary evaporation to give the crude product. After recrystallization from ethanol to give a white solid 7.23g, yield 76.8percent.
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 3 h; Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water for 1 h;
In an argon atmosphere, 10 g (29 mmol) of 1-(4-bromophenyl)-phenyl-1H-benzimidazole were dissolved into 100 mL of dehydrated THF, and the temperature of the solution was cooled to -78° C. Then, 20 mL of n-butyllithium (in hexane, 1.6 mol/L) were dropped. After the mixture had been stirred at -78° C for 1 hour, the temperature of the mixture was increased to 0°C. The temperature of the mixture was cooled to -78° C again, and 9.7 mL (87 mmol) of trimethoxyborane were dropped. The mixture was stirred at -78° C for 1 hour, and was then stirred at room temperature for 2 hours. 100 mL of 10-mass percent hydrochloric acid were added, and the whole was stirred for 1 hour, followed by filtration. The organic layer of the filtrate was washed with a saturated sodium chloride solution and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by means of silica gel column chromatography to obtain 4.2 g of 4-(2-phenyl-1H-benzimidazol-1-yl)phenylboronic acid (46percent yield).
1-[4-(10-naphthalene-2-yl-anthracene-9-yl)-phenyl]-2-phenyl-1H-benzimidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; toluene; for 7h;Heating / reflux;
(4) Synthesis of 1-[4-(10-naphthalene-2-yl-anthracene-9-yl) phenyl]-2-phenyl-1H-benzimidazole (Compound (9-7)) Dissolving 1.0 g (2.9 mmol) of <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benzimidazole</strong> obtained in the above step (3), 1.1 g (3.1 mmol) of 10-naphthalene-2-yl-anthracene-9-boronic acid and 0.1 g (0.09 mmol) of tetrakis (triphenylphosphine) palladium into 15 milliliter of 1,2-dimethoxyethane and 2 milliliter of toluene, adding 5 milliliter of 2.0M sodium carbonate aqueous solution, the resultant suspension was refluxed with heating for 7 hours. After completion of the reaction, separation with filtration was carried out and resultant crystals were washed with water and methanol, thereby obtaining 1.45 g of cream color solids (yield: 89 %). As a result of MS analysis, it was recognized that the cream color solids were identified as the aimed substance and that m/e= 572 for molecular weight of 572.23.
With toluene-4-sulfonic acid; In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 12h;
Fourth Step: Synthesis of Intermediate Product (D) (0133) 29.7 g (80.9 mmol) of the intermediate product (C) and 1.4 g (8.1 mmol) of p-toluenesulfonic acid were suspended in 300 mL of xylene and agitated at 150 C. for 12 hours. After cooling, xylene was removed under the reduced pressure to provide a solid, and the solid was recrystallized with methanol to provide 22.4 g (yield: 79%) of the intermediate product (D).
52%
With toluene-4-sulfonic acid; In xylene; for 3h;Heating / reflux;
2.1 g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl] benzamide were suspended into 30 mL of xylene, 0.6 g (2.9 mmol) of p-toluenesulfonic acid monohydrate was added, and the whole was refluxed under heating for 3 hours. After the resultant had been stood to cool, the reaction solution was added with ethyl acetate, dichloromethane, and water for filtering insoluble matter out. An organic layer was extracted from a mother liquor, washed with water and a saturated sodium chloride solution, and dried with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by means of silica gel column chromatography to obtain 1.0 g of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole (52% yield).
52%
With toluene-4-sulfonic acid; In xylene; for 3h;Heating / reflux;
(3) Synthesis of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole Suspending 2.1 g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl] benzamide obtained in the above step (2) into 30 milliliter of xylene, and adding 0.6 g (2.9 mmol) of p-toluenesulfonic acid 1 hydrate, the resultant solution was azeotropically dehydrated while refluxing with heating for 3 hours. After naturally cooling the reacted solution, ethyl acetate, dichloromethane and water were added to the reacted solution, followed by separating an insoluble substance by filtration. Extracting an organic layer from mother liquor, the organic layer was washed with water and a saturated solution of sodium chloride and then, dried with anhydrous sodium sulfate, followed by removing the solvent by distillation under reduced pressure. Refining the residue with silicagel column chromatography, 1.0 g of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole was obtained as white crystals with a slight pink color (yield: 52 %).
52%
toluene-4-sulfonic acid; In xylene; for 3h;Reflux;
(C-3) Synthesis of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole 2.1g (5.7 mmol) of N-[2-(4-bromophenylamino)phenyl]benzamide was suspended in 30 mL of xylene. To the resulting suspension, 0.6g (2.9 mmol) of p-toluenesulfonic acid monohydrate was added, and the resultant was subjected to azeotropic dehydration while heating under reflux for 3 hours. After allowing it to be cool, ethyl acetate, methylene chloride and water were added to the reaction solution, and unsoluble matters were filtered off. An organic phase was extracted from a mother solution, washed with water and saturated saline, and dried with anhydrous sodium sulfate. The solvent was distilled off under a reduced pressure. Residues were purified by silica gel column chromatography, whereby 1.0g of slightly pinky white crystals of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole were obtained (yield 52%).
at 250℃; for 3h;
(1) Synthesis of Intermediate Compound M6; 30 Grams of Intermediate Compound M6 were synthesized by using 1-fluoro-2-nitrobenzene and 1-bromo-4-aminobenzene as starting materials according to the method described in Chemistry of Materials, 2009, 21 (12), 2452.
30 g
at 250℃; for 3h;
As shown in synthetic route 4 below, 30 g of intermediate compound M5 was synthesized by a method described in a non-patent document: Chemistry of Materials, 2009, 21(12), 2452.
In an argon atmosphere, 10 g (29 mmol) of 1-(4-bromophenyl)-phenyl-1H-benzimidazole were dissolved into 100 mL of dehydrated THF, and the temperature of the solution was cooled to -78 C. Then, 20 mL of n-butyllithium (in hexane, 1.6 mol/L) were dropped. After the mixture had been stirred at -78 C for 1 hour, the temperature of the mixture was increased to 0C. The temperature of the mixture was cooled to -78 C again, and 9.7 mL (87 mmol) of trimethoxyborane were dropped. The mixture was stirred at -78 C for 1 hour, and was then stirred at room temperature for 2 hours. 100 mL of 10-mass% hydrochloric acid were added, and the whole was stirred for 1 hour, followed by filtration. The organic layer of the filtrate was washed with a saturated sodium chloride solution and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by means of silica gel column chromatography to obtain 4.2 g of 4-(2-phenyl-1H-benzimidazol-1-yl)phenylboronic acid (46% yield).
1-[4-(9,10-diphenylanthracen-2-yl)-phenyl]-2-phenyl-1H-benzimidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux;
1.0 g (2.9 mmol) of <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benzimidazole</strong>, 1.2 g (3.2 mmol) of 9,10-diphenylanthracene-2-boronic acid, and 0.067 g (0.058 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 1. 6 g of a greenish white solid (90% yield) . Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 598 with respect to a molecular weight of 598.24.
1-[4-[9,10-di(2-naphtyl)anthracen-2-yl]phenyl]-2-phenyl-1H-benzimidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Heating / reflux;
1.0 g (2.9 mmol) of 1-(4-bromophenyl)-2-phenyl-1H-benzimidazole, 1.5 g (3.2 mmol) of 9,10-di(2-naphtyl)anthracene-2-boronic acid, and 0.067 g (0.058 mmol) of tetrakis(triphenylphosphine)palladium were dissolved into 20 mL of 1,2-dimethoxyethane. Then, 10 mL of a 2 M aqueous solution of sodium carbonate were added, and the whole was refluxed under heating for 8 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered, and the resultant solid was washed with water, methanol, and toluene to obtain 1.7g of a greenish white solid (84% yield) . Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 698 with respect to a molecular weight of 698.27.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 12h;
Fifth Step: Synthesis of Intermediate Product (E) (0135) 22.4 g (64.1 mmol) of the intermediate product (D), 19.6 g (77.0 mmol) of bis(pinacolato)diboron, 1.3 g (1.6 mmol) of [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (II), and 18.9 g (192.3 mmol) of potassium acetate were suspended in 230 mL of dimethylformamide and agitated at 80 C. for 12 hours. After cooling, the reaction solution was poured in distilled water to deposit a solid, which was filtered and separated. The filtered solid was recrystallized with ethyl acetate/hexane to provide 24.4 g (yield: 96%) of intermediate product (E).
72.7%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 4h;Inert atmosphere;
Under a nitrogen atmosphere, 5.0 g (14.3 mmol) intermediate compound M5, 4.0 g (15.8 mmol) of bis- dioxaborolane, 4.2 g (42.8 mmol) of potassium acetate, and 0.58 g (0.71 mmol) of [1,1'- bis (diphenylphosphino) ferrocene ] palladium ( II ) dichloride dichloromethane adduct were added to 100 mL of N,N- dimethylformamide in a 300-mL three-neck flask and were heated to 80C and then stirred at the same temperature for 4 hours. [0177 ] The mixture was cooled to room temperature and 100 mL of water added thereto. The mixture was stirred for 1 hour and was then filtered. The resulting solid residue was slurry-washed with water to give crude crystals of intermediate compound M6. [ 0178 ] The resulting crude crystals were dissolved in toluene. The solution was purified by column chromatography (toluene/ethyl acetate = 4/1), followed by recrystallization from a solvent mixture of toluene/heptane = 4:1. The resulting crystals were dried under reduced pressure to give 4.12 g (yield: 72.7%) of intermediate compound M6.
43%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃; for 12h;Inert atmosphere; Schlenk technique;
General procedure: A mixture of 1a (0.70 g , 2.0 mmol), bis(pinacolate)diborane (0.53 g, 2.1 mmol), l,l'-bis(diphenylphosphino)ferrocene]dichloropalladium (Pd(dppf)Cl2) (0.060g,0.08mmol), andanhydrous potassium acetate (0.393 g, 4.0 mmol) in 1,4-dioxane(20 mL) was heated at 80C under nitrogen for 12 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (30 mL*3). The organic extracts were washed with water, brine, and then dried with anhydrous MgSO4. After filtration, the filtrate was pumped dry in vacuo. The crude residue was subjected to column chromatography by eluting with hexanes/EA (8:1) as the eluent to give a white solid (yield: 81%).
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 80℃; for 3h;Inert atmosphere;
SYNTHESIS EXAMPLE 1 (Synthesis of Compound 1); Into a 100-mL three-necked flask, 3.0 g (8.6 mmol) of <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benzimidazole</strong>, 2.2 g (8.7 mmol) of bis(pinacolato)diboronic acid, 0.21 g (0.29 mmol) of [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium (II), 2.5 g (25 mmol) of potassium acetate, and 50 ml of DMF were charged and the mixture was heated at 80 C for 3 h in argon flow. After confirming the disappearance of the starting boron compound, the mixture was cooled to room temperature. After adding 2.2 g (8.6 mmol) of 9-bromophenanthrene, 0.21 g (0.29 mmol) of [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium (II), and 21 mL of a 2 M aqueous solution of sodium carbonate, the mixture was further heated at 80 C for 3 h under stirring. After the reaction, water was added. The precipitated crystals were corrected by filtration, washed with water and methanol, and dried under reduced pressure, to obtain a crude reaction product, which was then purified by a column chromatography (silica gel, dichloromethane: hexane), to obtain 2.5 g of white crystals. The obtained crystals were identified to Compound 1 by FD-MS (field desorption mass spectrometry). Yield: 65%.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 120 - 150℃; for 10h;Inert atmosphere;
General procedure: Intermediate IV was prepared by the synthesis method of Intermediate B1, and the specific structure is shown in Table 2 below (3) in 500mL three-necked flask,Purged with nitrogen,0.05 was added as an intermediate N1 to 300 ml of N, N-dimethylformamide (DMF)0.06 mol of bis (pinacolato) diboron,0.0001 mol (1,1'-bis (diphenylphosphino) ferrocene) dichloropalladium (II) and 0.125 mol of potassium acetate were added,The mixture was stirred,The mixed solution of the above reactants was heated to reflux for 10 hours at a reaction temperature of 120-150 C;After the reaction was over, 200 ml of water was cooled and added, and the mixture was filtered and dried in a vacuum oven.The obtained residue was separated and purified on a silica gel column to obtain Compound Intermediate B1;HPLC purity 99.5%, yield 84.1%.
In 2-methoxy-ethanol; for 12h;Inert atmosphere; Schlenk technique; Reflux;
A mixture of benzaldehyde (2.02 g, 19.0 mmol) and N-phenylbenzene-1,2-diamine (1.0 g, 5.43 mmol) was dissolved in 2-methoxyethanol (10 mL). Then the mixture was heat to reflux for 12 h. The solvent was removed and the residue was extracted with dichloromethane (30 mL x 3). The organic layer was washed with water, brine and then dried with anhydrous MgSO4, filtered. After filtration, the filtrate was pumped dry in vacuo. The crude residue was subjected to silica gel column chromatography by eluting with hexanes: dichloromethane (1:1) as an eluting to give a brown solid (yield: 43%).1H NMR (400 MHz, acetone-d6,):delta (ppm) 7.88 (d, J = 8.8 Hz, 3 H), 7.62-7.60 (m, 2 H), 7.42-7.38 (m, 5H), and 7.38-7.25 (m, 3 H); Mass (FAB): m/z: 351.0 [M+H]+.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Inert atmosphere; Reflux;
Example 11 In the atmosphere of argon, 2.7g of fluoranthene-3-boronic acid, 3.5g of <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benzimidazole</strong> which was synthesized in Synthesis Example 3, 0.231g of tetrakis(triphenylphosphine)palladium(0), 40 mL of dimethoxyethane and 20 mL of a 2M aqueous sodium carbonate solution were placed in a flask.
3-bromo-7,9-diphenyl-8H-cyclopenta[a]acenaphthylen-8-one[ No CAS ]
[ 1415106-04-5 ]
[ 1415106-01-2 ]
Yield
Reaction Conditions
Operation in experiment
(3) Synthesis of Intermediate Compounds M3 (M3-1 and M3-2); Under a nitrogen atmosphere and room temperature, the following reagents and solvent were loaded into a 1-L three-necked reaction vessel. Intermediate Compound M2:18.0 g (41.3 mmol) Intermediate Compound M1:14.0 g (53.8 mmol) Isoamyl nitrite:8.72 g (74.4 mmol) Toluene:720 mL Next, the reaction solution was heated to 95C, and then the reaction solution was stirred at the temperature (95C) for 1.5 hours. Next, the reaction solution was cooled, and then the reaction solution was washed with 1 L of water three times. Next, an organic layer obtained by the washing with water was further washed with a saturated salt solution, and was then dried with magnesium sulfate. Next, a filtrate obtained by filtering the organic layer was concentrated under reduced pressure. Thus, a dark brown liquid was obtained. Next, the resultant dark brown liquid was purified by column chromatography (eluent: toluene/heptane=1/3). Next, a solution obtained during the purification was concentrated under reduced pressure. Thus, a crystal was obtained. Next, 345 mL of methanol were added to the resultant crystal, and then the mixture was subjected to slurry washing by heating. After that, the washed product was left standing to cool to room temperature. A crystal produced at the time of the cooling was filtered. Thus, 21.9 g of a yellow crystal, Intermediate Compounds M3, as a mixture of isomers (M3-1 and M3-2) were obtained (yield: 87%).; (4) Synthesis of Intermediate Compounds M4 (M4-1 and M4-2); Under a nitrogen atmosphere, the following reagents and solvent were loaded into a 1-L three-necked vessel. Intermediate compounds M3 (mixture of M3-1 and M3-2): 19.4 g (31.9 mmol) Bis-dioxabororane: 16.2 g (63.9 mmol) Potassium acetate: 6.27 g (63.9 mmol) Tetrakistriphenylphosphine palladium: 1.107 g (0.96 mmol) DMSO: 388 mL Next, the reaction solution was heated to 100C, and then the reaction solution was stirred under the temperature (100C) for 1.5 hours. Next, the reaction solution was cooled to 30C, and then 400 mL of methanol were added to the reaction solution. Next, the reaction solution was cooled to 10C, and then the reaction solution was stirred under the temperature (10C) for 1 hour. After that, filtration was performed. Next, 800 mL of methanol were added to the cake obtained by the filtration, and then the mixture was subjected to slurry washing by heating for 1 hour while the solvent (methanol) was refluxed. After that, the washed product was cooled to room temperature and then filtered. Thus, 18.3 g of a crude crystal of Intermediate Compounds M4 were obtained (yield: 87.5%). Next, a solution prepared by dissolving the resultant crude crystal in 265 mL of toluene was purified by column chromatography (eluent: toluene/heptane=1/2?toluene/heptane=1/1). Next, the purified product was subjected to slurry washing by heating with a toluene/methanol mixed solvent. Thus, 9.75 g of a yellow crystal, Intermediate Compounds M4, as a mixture of isomers (M4-1 and M4-2) were obtained (yield: 46.6%).; (2) Synthesis of Exemplified Compounds D87 and D88; Under a nitrogen atmosphere, the following reagents and solvents were loaded into a 200-mL three-necked flask. Intermediate Compounds M4 (the mixture of M4-1 and M4-2) : 1.30 g (1.99 mmol) Intermediate Compound M6: 1.54 g (1.39 mmol) Toluene: 39 mL Ethanol: 13 mL Sodium carbonate: 0.42 g (3.97 mmol) Water: 13 mL Tetrakistriphenylphosphine palladium: 0.12 g (0.11 mmol) Next, the reaction solution was heated to 70C, and then the reaction solution was stirred under the temperature (70C) for 5 hours. Next, the reaction solution was left standing to cool to room temperature. After that, the reaction solution was washed with 100 mL of water three times. Thus, an organic layer was obtained. Next, the organic layer was dried with magnesium sulfate. After that, a filtrate obtained by filtering the solution was concentrated under reduced pressure. Thus, a yellow crude crystal was obtained. Next, a solution obtained by mixing the resultant crude crystal and 19 mL of toluene was purified by column chromatography (eluent: toluene/ethyl acetate=9/1?toluene/ethyl acetate=5/1). Next, the solution was concentrated. After that, methanol was added to the concentrated product, and then the mixture was subjected to slurry washing by heating. Thus, 0.96 g of a mixture of Exemplified Compounds D87 and D88 as a yellow crystal were obtained (yield: 58%). It should be noted that Exemplified Compound D87 is synthesized from Intermediate Compound M4-1 and Exemplified Compound D88 is synthesized from Intermediate Compound M4-2. Mass spectrometry confirmed 796 as the M+ of the compound. In addition, NMR measurement confirmed that the mixing ratio between Exemplified Compounds D87 and D88 was 1:1. 1H-NMR (CDCl3): delta (ppm)=8.21 (s, 1H), 8.20 (s, 1H), 7.93-7.63 (m, 38H), 7.43-7.29 (m, 28H), 6.59 (dd, 2H, J1=7.99 Hz, J2=3.99 Hz), 6.35 (d, 2H, J=7.99 Hz) Further, the ...
benzofurano[3,2-b]dibenzofuran-6-boronic acid[ No CAS ]
[ 1377469-09-4 ]
Yield
Reaction Conditions
Operation in experiment
97%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 13h;Reflux;
A mixture of 3.00g of <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benz[d]imidazole</strong>, 3.70g of benzofurano[3,2-b]dibenzofuran-6-boronic acid, 0.60g of tetrakis(triphenylphosphine)palladium(0), 26 ml of 1,2-dimethoxyethane and 13 mL of a 2M aqueous sodium carbonate solution were refluxed for 13 hours. The reaction mixture was cooled to room temperature, and water was added thereto, followed by stirring for 30 minutes. The generated solids were collected by filtration, washed with water, methanol and hexane, and dried under reduced pressure. The solids obtained were purified by silica gel chromatography, whereby 4.42g of white solids were obtained. As a result of mass spectroscopy analysis, the compound obtained was identified as the following compound 2 (m/e=526 for molecular weight 526.17). The yield was 97%.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 6h;Reflux;
A mixture of 1.36g of 1-(4-bromophenyl)-2-phenyl-1 H-benz[d]imidazole, 1.47g of 2-(benzo[kl]xanthene-4-yl)-4,4,5,6-tetramethyl-1,3,2-dioxaborolane, 0.14g of tetrakis(triphenylphosphine)palladium(0), 12 ml of 1,2-dimethoxyethane and 6 mL of 2M aqueous sodium carbonate solution were refluxed for 6 hours. The reaction mixture was cooled to room temperature, and water was added thereto, followed by stirring for 30 minutes. The generated solids were collected by filtration, washed with water, methanol and hexane, and dried under reduced pressure. The solids obtained were purified by silica gel chromatography, whereby 1.67g of white solids were obtained. As a result of mass spectroscopy analysis, the compound obtained was identified as the following compound 3 (m/e=486 for molecular weight 486.17). The yield was 88%.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 8h;Reflux;
A mixture of 3.00g of 1-(4-bromophenyl)-2-phenyl-1 H-benz[d]imidazole, 2.94g of benzo[b]naphtho[2,1-d]furan-5-boronic acid, 0.50g of tetrakis(triphenylphosphine)palladium(0), 26 ml of 1,2-dimethoxyethane and 13 mL of a 2M aqueous sodium carbonate solution were refluxed for 8 hours. The reaction mixture was cooled to room temperature, and water was added thereto, followed by stirring for 30 minutes. Ethyl acetate and hexane were added to the resulting solution, followed by stirring further for 30 minutes. The generated solids were collected by filtration, washed with water, methanol and hexane, and dried under reduced pressure. The solids obtained were dispersed and washed with a mixed solution of hexane/ethyl acetate. After that, the solids were purified by silica gel chromatography and dispersed and washed in hot toluene, whereby 3.01g of white solids was obtained. As a result of mass spectroscopy analysis, the compound obtained was identified as the following compound 1 (m/e=486 for molecular weight 486.17). The yield was 72%.
9-(4-(2-phenyl-1H-benzo[d]imidazol-1-yl)phenyl)-9H-carbazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With copper(l) iodide; 18-crown-6 ether; potassium carbonate; at 170℃; for 48h;Inert atmosphere;
10067] In a dry flask of 50 ml, carbazole (1.5 g, 9 mmol), C-phenyl- 1 -p-bromophenyl benzimidazole (2.78 g, 8.0 mmol), cuprous iodide (0.046 g, 0.24 mmol), 18-crown ether-6 (0.064 g, 0.24 mmol) and potassium carbonate (5.53 g, 40.0 mmol) are dissolved into DMPU (2 ml), heated to 170 C., heated to 170 C. under the protection of nitrogen gas and reacted for two days. After filtration, an organic solvent and water are used respectively for washing, and finally 2.4 g of a white product is obtained by colunm chromatography and the yield thereof is 90%.10068] Physical and chemical parameters of the white product are: ?H-NMR:(CDC13, 600 MHz): oe(ppm) 8.278. 29 (m, 1H), 7.897.94 (dd, J=6 Hz, 3H), 7.657.68 (m, 2H), 7.44.-7.45(d, J=6 Hz, 1H), 7.257.28 (m, 1H), 7.01.-7.10 (m, 5H), 6.826.89 (m, 4H), 6.766.78 (t, J=12 Hz, 2H), 6.306.31 (d, J=6 Hz, 2H). ?3C-NMR (150 MHz, CDC13): oe139.81, 136.34, 133.97, 131.18, 128.69, 128.31, 127.85,127.74, 125.62, 124.46, 123.56, 1.23.26, 119.91, 119.41,110.29, 109.83. MS (APCI): calcd for C3,H2,N3, 435.17; found,436.2 (M+1). Anal. calcd for C3,H2,N3 (%): C 85.34, H 4.93, N 9.73; found: C 85.90, H 4.20, N 9.90, from which it can be verified that 4-carbazolyl-C-phenyl benzimidazolyl benzene is included.
diphenyl(4-(2-phenyl-1H-benzo[d]imidazol-1-yl)phenyl)phosphine oxide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
2-phenyl-N-p-bromophenylbenzimidazole (1.0mmol) was dissolved in THF (tetrahydrofuran) (50 ml), Cooling to -78 C, Add n-BuLi (1.1mmol), Reaction 1 hour. then add chlorodiphenylphosphine (1.2mmol), raising the temperature to room temperature reaction 12 hours. Add methanol to quench the reaction. At the same time, add 30% H2O2 aqueous solution (5 ml) oxidization to obtain 4 - (1 - methyl-imidazolyl) - trityl-phosphorus-oxygen (pNBIPO); yield: 70%.
1000 ml three-neck bottle with electric stirring, Ar gas protection, adding the second step reaction product 35.5g (molecular weight 262, 0.13mol), benzoyl chloride 19.6g (molecular weight 140, specific gravity 1.212, 0.14mol), N-methyl Pyrrolidone (NMP) 350 ml, stirred at room temperature for 90 minutes, stirred at 50 C for 2 hrs, poured into 1000 ml of water, stirred, salted out and filtered off.The solid was heated to 130 C under the protection of Ar gas, and water was discharged (the water separator was installed in the device), and reacted at 250 C for 3 hours. The water was clearly separated and placed under room temperature with Ar gas protection. CHCl3Extraction, separation by column chromatography, ethyl acetate elution afforded 37.3 g of pale white solid, molecular weight 348, HPLC 99.62%, yield 82.2%.
55.9%
Synthesis of Intermediate 5-C: To a 500ml three-necked round flask with magnetic stirrer was sequentially added with Intermediate 5-B (15.8g, 0.06mol), benzoyl chloride (11.2g, 0.08mol), N-methylpyrrolidone 200ml. After the reaction was stirred at room temperature for 2h, it is continued to warm to 50-60C and was stirred for 2h. After the reaction solution was poured into 200ml of water, the precipitated solid was filtered. After drying under an argon atmosphere and heated to 130C, water is generated, and the reaction at 250C for 3 hours. Cooled to room temperature, extracted with CH2Cl2 to obtain a crude product. The crude product was purified by column chromatography on silica gel, ethyl acetate / petroleum ether as eluent to give 11.7g pale yellow solid, yield 55.9%.
In a 1000 ml three-necked flask, equipped with mechanical stirring, Ar gas protection, add 25. lg of the bromine synthesized in the third step (molecular weight 348, 0.072 mol 1), 300 ml of anhydrous THF, cooled to -78 C, stirred 35ml of BuLi (2 · 4M, 0.084mol) was added dropwise, the temperature was maintained at _78 C, and after stirring for 10 min, 40 ml of B(0iPr) 3 (molecular weight 188.07, specific gravity 0.9574, 0.204 mol) was added dropwise at -78 C. After stirring to room temperature (with 3 hrs), dilute acid is added to hydrolyze, the aqueous layer is separated, neutralized to neutrality, sodium chloride is added, hydrazine HF dissolved in water is distilled off under reduced pressure, and a white solid is precipitated and filtered to obtain a product. 21 g of solid product, yield 93.41%.
80%
Under nitrogen protection,In a 1000ml three-neck bottle,30 g (85.96 mmol, 1 eq) of the compound 1- (4-bromophenyl) -2-phenyl-1H-benzo [d] imidazole was added to 300 mL of tetrahydrofuran,Cooling down to minus 78 degrees,39.4 mL (94.56 mmol, 1.1 eq) of n-BuLi was slowly added dropwise to the above reaction solution,Incubation reaction for 1.5h,Subsequently, 32.3 g (171.92 mmol, 2 eq) of triisopropyl borate was slowly added dropwise to the above reaction solution,Naturally warmed to room temperature and stirred overnight to stop the reaction,Add 100 mL of a 1 mol / L dilute hydrochloric acid solution and stir at room temperature for 1 h.The layers were separated, and the aqueous phase was extracted with 200 mL of dichloromethane * 1. The organic phases were combined.Spin-drying gave 21.67 g of a white solid with a yield of 80%.
76.8%
With n-butyllithium; In tetrahydrofuran; at -78℃;
Synthesis of Intermediate 5-D: In a 250ml three-necked round flask, added was Intermediate 5-C(11.5g, 0.03mol), and 120ml dried THF that underwent treatment with Na /Benzophenone. Liquid nitrogen was used to cool reaction to -78C. While stirring, slowly added dropwise 14.5ml of n-butyllithium (0.036mol, 2.5mol·L-1), and Triisopropyl borate 9.96ml (8.12g, 0.043mol). After the addition was completed, stirred to room temperature. Adding an appropriate amount of dilute hydrochloric acid, hydrolysis, extraction with ethyl acetate, the combined organic phases. The organic solvent was removed by rotary evaporation to give the crude product. After recrystallization from ethanol to give a white solid 7.23g, yield 76.8%.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 5h;
Intermediate I-3 4.23 g (11.0 mmol), Intermediate I-4 3.49 g (10.0 mmol), Pd (PPh3) 4 0.06 g (0.5 mmol) and K2CO34.15 g (30.0 mmol) of THF/H2O (2/1 volume ratio) mixed solution and then dissolved in 40 mL, was stirred at 80 for 5 hours. after cooling to room temperature the reaction solution was added to 40 mL water and extracted three times with diethyl ether, 50 mL. The combined organic layers were dried over magnesium sulfate, and separation of the residue obtained by evaporation of the solvent by silica jelgwan chromatography to give the compound 4 4.33 g (yield 81%). The resulting compound was confirmed by LC-MS and 1H NMR.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; for 2h;Reflux;
Subsequently, the following reagents and solvents were added into the reaction vessel.2.40 g (5.2 mmol, 1.1 eq) of 2-pinacolate-6,12-dinaphthylchrysene:Intermediate Compound M2: 1.66 g (4.7 mmol, 1.0 eq)Toluene: 75 mLSodium carbonate aqueous solution: 25 mL (3.0 eq)Then, while stirring the reaction solution, the following reagents were further added.Pd (PPh3) 4: 274 mg (0.24 mmol, 0.05 eq)Ethanol: 25 mLSubsequently, the reaction solution was stirred for 2 hours while heating and refluxing. After completion of the reaction, the reaction solution was cooled. Subsequently, liquid separation operation was performed using water, and the organic layer was recovered. Subsequently, the obtained organic layer was concentrated under reduced pressure. Thus, a crude product was obtained. Subsequently, the resulting crude product was purified by silica gel column chromatography (eluent: toluene / ethyl acetate = 10/1), and the separated solution was concentrated under reduced pressure. Thus, a solid was obtained. Then, the resulting solid was subjected to slurry cleaning with methanol, followed by filtration. Thus, 2.82 g of the exemplified compound A11 (yield: 86.8%, HPLC purity: 99.8%) was obtained.
diphenyl(4-(2-phenyl-1H-benzo[d]imidazol-1-yl)phenyl)phosphine oxide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
Step S101: 2-phenyl-4-N-p-bromophenylbenzimidazole was dissolved in THF (tetrahydrofuran); preferably,In the step, 2-phenyl-4-N-p-bromophenylbenzimidazole was 1. Ommol, THF (tetrahydrofuran)Step S102: cooling to -78 C, adding n-butyllithium, for one hour; preferably, n-butyllithium is 1 · lmmol in this step;Step S103: Diphenylphosphonium chloride is added and the temperature is raised to room temperature for 12 hours. Preferably, diphenylphosphonium chloride is 1.2 mmol in this step;Step S104; adding a methanol quenching reaction while adding 30% H2O2 aqueous solution to give 4- (1-methylbenzimidazolyl) -triphenylphosphine oxide; preferably, 30% H2O2 aqueous solution in this step is 5 ml ; Yield: 70%
With tris(dibenzylideneacetone)dipalladium (0); tri-tert-butyl phosphine; In toluene; for 5h;Reflux;
Synthesis Example 13: Compound A78 (0365) Pd(dba)3 (0.03 eq), (t-Bu)3P (0.06 eq), and toluene (based on a reagent (0.1 M 1 eq)) were added to a flask containing Int B-2 (1 eq) and R?-4 (1.2 eq) to form a mixed solution, and then, the mixed solution was stirred under reflux for 5 hours. After the reaction solution was cooled to room temperature, an extraction process was performed thereon using MC, followed by a washing process performed thereon using distilled water. Then, the resulting product obtained from the washing process was subjected to a drying process using MgSO4 and a vacuum distillation process. The residue obtained therefrom was purified by column chromatography, thereby completing the preparation of Compound A78 (yield: 71.9%). (0366) HRMS for C37H23N3S [M]+: calculated: 541.67, found: 540. (0367) Elemental Analysis for C37H23N3S calculated: C, 82.04; H, 4.28; N, 7.76; S, 5.92
With tris(dibenzylideneacetone)dipalladium (0); tri-tert-butyl phosphine; In toluene; for 5h;Reflux;
Synthesis Example 15: Synthesis of Compound A82 (0371) Pd(dba)3 (0.03 eq), (t-Bu)3P (0.06 eq), and toluene (based on a reagent (0.1 M 1 eq)) were added to a flask containing Int C-2 (1 eq) and R?-4 (1.2 eq) to form a mixed solution, and then, the mixed solution was stirred under reflux for 5 hours. After the reaction solution was cooled to room temperature, an extraction process was performed thereon using MC, followed by a washing process performed thereon using distilled water. Then, the resulting product obtained from the washing process was subjected to a drying process using MgSO4 and a vacuum distillation process. The residue obtained therefrom was purified by column chromatography, thereby completing the preparation of Compound A82 (yield: 74.9%). (0372) HRMS for C37H23N3O [M]+: calculated: 525.61, found: 524. (0373) Elemental Analysis for C37H23N3O calculated: C, 84.55; H, 4.41; N, 7.99; O, 3.04
With tris(dibenzylideneacetone)dipalladium (0); tri-tert-butyl phosphine; In toluene; for 5h;Reflux;
Synthesis Example 17: Synthesis of Compound A86 (0377) Pd(dba)3 (0.03 eq), (t-Bu)3P (0.06 eq), and toluene (based on a reagent (0.1 M 1 eq)) were added to a flask containing Int D-4 (1 eq) and R?-4 (1.2 eq) to form a mixed solution, and then, the mixed solution was stirred under reflux for 5 hours. After the reaction solution was cooled to room temperature, an extraction process was performed thereon using MC, followed by a washing process performed thereon using distilled water. Then, the resulting product obtained from the washing process was subjected to a drying process using MgSO4 and a vacuum distillation process. The residue obtained therefrom was purified by column chromatography, thereby completing the preparation of Compound A86 (yield: 75%). (0378) HRMS for C40H29N3[M]+: calculated: 551.69, found: 550. (0379) Elemental Analysis for C40H29N3 calculated: C, 87.08; H, 5.30; N, 7.62
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 11h;Reflux;
In a one-neck 250 mL flask2.5 g (4.54 mmol) of Intermediate 4, 1.59 g (4.54 mmol) of Int.4, 0.16 g (0.14 mmol) of Pd (PPh3) 4, 1.26 g (9.08 mmol) of K2CO3,50 mL of toluene, 20 mL of ethanol and 10 mL of water were mixed and stirred for 11 hours while heating and refluxing.After the reaction was completed, the solvent was distilled off under reduced pressure, diluted with 50 mL of CHCl3 and filtered using celite.Washed with 100 mL of CHCl3, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 2.0 g (yield: 64.5%) of 4-42 (WS15-30-305) as a white solid.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene;Reflux;
In one 250 mL flask, 2.4 g (5.00 mmol) of Int.16, 1.9 g (5.50 mmol) of intermediate (13) 0.06 g (0.50 mmol) of Pd(PPh3)4, 0.7 g (12.5 mmol) of K2CO3, 50 mL of toluene, 25 mL of EtOH and 25 mL of H2O were mixed and then refluxed. After the reaction is complete, cool to room temperature and add 200 mL H2O. The mixture was extracted twice with 300 mL of dichloromethane (DCM), the extract was dried with Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The solid was dissolved in chloroform and purified by silica gel column chromatography (dichloromethane (DCM) / ethyl acetate (EA)). Solidification with dichloromethane (DCM) / n-hex and filtration gave 1.3 g (yield: 43.3%) of compound 4-418 (WS16-30-067) as a beige solid.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 70℃; for 8h;Inert atmosphere;
500 ml three-neck bottle,Equipped with mechanical mixing and distillation unit,5.0 g (0.0091 mol) of the compound of the formula M-206 was added,3.49 g (0.0101 mol) of 4-(2-phenyl-1H-benzo[d]imidazol-1-yl)bromobenzene,40 ml of toluene,40 ml of ethanol,25 ml of water,2.51 g (0.0182 mol) of potassium carbonate,0.05 g (0.0000455 mol) of tetrakistriphenylphosphine palladium was added under nitrogen protection.After the addition, slowly warmed to 70 C,Reaction for 8 hours.Cool down, add water,The organic layer is washed,Dry over anhydrous sodium sulfate,Decolorization on silica gel column,The eluent is concentrated to dryness.The crude product P-2 was obtained.The above crude P-2 product was recrystallized from a mixed solvent of toluene and ethyl acetate to obtain 5.01 g of a product P-2.The yield was 71.3%.
2- [5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-biphenyl-3-yl]-4,6-diphenyl-1,3,5-triazine[ No CAS ]
4,6-diphenyl-2- [4-(2-phenylbenzoimidazol-1-yl)-1,1':3',1"-terphenyl-5'-yl]-1,3,5-triazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; at 65℃; for 8h;
Under a nitrogen stream, Synthesis Example 2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl} -biphenyl-3-yl] -4,6- diphenyl- 1,3,5-triazine(1.50 g, 2.93 mmol),1- (4-bromophenyl) -2-phenylbenzimidazole (1.13 g, 3.27 mmol),4 M aqueous sodium hydroxide solution (2.20 mL, 8.80 mmol),And tetrakis (triphenylphosphine) palladium (0.10 g, 0.088 mmol) were added to TetrahiDrofuran (30 mL) was suspended and stirred at 65 C. for 8 hours. The resulting reaction solution was allowed to cool to room temperature, and the precipitate was collected by filtration. The precipitate collected by filtration was washed successively with pure water and methanol to obtain a gray powderWas obtained. The obtained gray powder was purified by recrystallization from toluene to obtain the desired product4,6-diphenyl-2- [4- (2-phenylbenzoimidazolyl-1-yl) -1,1 ': 3', 1 "- terphenyl-5'-yl] -1,3,5-triazine(Yield: 1.17 g, yield 61%, LC purity 99.00%) as a white powder (A-59).
2-[3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,6-diphenyl-1,3,5-triazine[ No CAS ]
1-[3'-chloro-5'-(4,6-diphenyl-1,3,5-triazin-2-yl)-[1,1'-biphenyl]4-yl]-2-phenyl-1H-1,3-benzodiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 65℃; for 12h;Inert atmosphere;
Under nitrogen stream, a solution of 2- [3-chloro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] -4 obtained in Synthesis Example 3, 6-Diphenyl-1,3,5-triazine(6.00 g, 12.8 mmol), 1- (4-bromophenyl) -2-phenylbenzimidazole (4.91 g, 14.0 mmol)Tetrakis (triphenylphosphine) palladium (0.443 g, 0.383 mmol) and 2 M aqueous tripotassium phosphate solution (19.2 mL, 38.3 mmol) were suspended in tetrahydrofuran (130 mL) and stirred at 65 C. for 12 hours . After allowing to cool, the precipitate was collected by filtration. The collected precipitate was washed successively with pure water and methanol to obtain a gray powder. The obtained gray powder was purified by recrystallization from toluene to obtain the desired product4,6-diphenyl-2- [3-chloro-5 - {(2-phenylbenzoimidazolyl- 1 -yl) - biphenyl-3-yl}] - 1,3,5-triazineOf a gray powder (yield 5.58 g, yield 71%, LC purity 99.52%).
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; In water; toluene; at 100℃; for 12h;
A 500-mL recovery flask was charged with Reactant A (1.2 eq), intermediate B or C (1.0 eq), tris (dibenzylideneacetone) dipalladium (0) (Pd2 (dba)3) (0.005 eq), SPhos (0.02 eq), toluene / ethanol (0.5 M, v / v = 10/1) and 3.0 M K2CO3 aqueous solution and stirred at 100 C for 12 hours under a stream of nitrogen gas. Here, by varying the equivalents of reactant A / B and catalyst, mono- and bis-coupled products can be obtained selectively. When the reaction was complete, water and toluene were added to the reaction. Then, the organic layer was recovered through a solvent extraction step, and dried over sodium sulfate. Thereafter, the solvent was distilled under reduced pressure to remove the solvent from the organic layer, and the resulting residue was purified by silica gel column chromatography. The resulting residue was recrystallized from toluene and a white solid was obtained as a novel compound of the present invention.
In 2-ethoxy-ethanol; water; for 24h;Reflux; Inert atmosphere;
In an inert gas atmosphere,the ligand <strong>[760212-58-6]1-(4-bromophenyl)-2-phenyl-1H-benzo[d]imidazole</strong> (57.3 mmol, 20.0 g) was added to a round bottom flask.Iridium trichloride trihydrate (26mmol, 9.2g),ethylene glycol monoethyl ether 300ml and water 100ml,the temperature was raised to reflux the system and the reaction was carried out for 24 hours. After the reaction was completed, water was added to precipitate the product, which was filtered and dried. The crude product was used in the next step without purification.
7 g of 1-(4-bromophenyl)-2-phenylbenzimidazole (0.02 mol) was added to 150 ml of THF, and the temperature was lowered to -78 C, and 12 ml (2.5 M/L, 0.03 mol) was added dropwise at -78 C. n-BuLi, keep warm for 30 minutes, add 4.26g (0.041mol) of trimethyl borate, after 2 hours of reaction, the reaction is completed, add 50ml of water to the reaction solution, stir for 20 minutes, add hydrochloric acid to adjust the pH to acidity, stir 30 The reaction solution was extracted three times with ethyl acetate. The organic layer was combined and washed with water, and then the organic phase was separated and evaporated to dryness. The solid was digested twice with petroleum ether and filtered to give 2 g of white solid intermediate A, yield 60%.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃; for 4h;
10 Preparation of compound 1
General procedure: In one neck round bottom flask (One neck r.b.f)9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-4-yl)-9H-carbazole (7.2 g, 15.6 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (5 g, 18.8 mmol), tetrakis (triphenylphosphine) palladium (0) (1.8 g, 1.56 mmol), potassium carbonate (4.3 g, 31.2 mmol), 1,4-dioxane/water(100ml/25ml) The mixture was refluxed at 120°C for 4 hours.After filtering at 120° C., it was washed with 1,4-dioxane, distilled water, and MeOH to obtain compound 1 (G). (6.6 g, 75%)
65%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃; for 4h;
Preparation of Compound 1
General procedure: In a one neck round bottom flask, a mixture of 9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-4-yl)-9H-carbazole (7.2 g, 15.6 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (5 g, 18.8 mmol), tetrakis(triphenylphosphine)palladium(0) (1.8 g, 1.56 mmol), potassium carbonate (4.3 g, 31.2 mmol) and 1,4-dioxane/water (100 ml/25 ml) was refluxed for 4 hours at 120° C. After filtering at 120° C., the result was washed with 1,4-dioxane, distilled water and MeOH to obtain Compound 1(C) (6.6 g, 75%).
65 %
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃;
2 Preparation of compound 2-1
General procedure: 9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-4-yl)-9H-carbazole 7.2 g, 15.6 mmol),2-Chloro-4,6-diphenyl-1,3,5-triazine (5 g, 18.8 mmol),Tetrakis(triphenylphosphine)palladium(0) (1.8 g, 1.56 mmol),A mixture of potassium carbonate (4.3 g, 31.2 mmol) and 1,4-dioxane/water (100 mL/25 mL) was refluxed in a round bottom flask at 120°C for 4 hours.Thereafter, the mixture was filtered at 120 °C,And then with 1,4-dioxane,Washed with distilled water and MeOH to obtain compound 2-1(C).(6.6 grams, 75%)
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃; for 4h;
Preparation of Compound 129
General procedure: In a one neck round bottom flask, a mixture of 9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-3-yl)-9H-carbazole (6.5 g, 14.1 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (4.54 g, 16.9 mmol), M tetrakis(triphenylphosphine)palladium(0) (1.6 g, 1.41 mmol), potassium carbonate (3.9 g, 28.2 mmol) and 1,4-dioxane/water (80 ml/28.2 ml) was refluxed for 4 hours at 120° C. After filtering at 120° C., the result was washed with 1,4-dioxane, distilled water and MeOH to obtain Compound 129(F) (5.4 g, 68%).
65%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃; for 4h;
11 Preparation of compound 129
General procedure: In one neck round bottom flask (One neck r.b.f)9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-3-yl)-9H-carbazole (6.5 g, 14.1 mmol),2-chloro-4,6-diphenyl-1,3,5-triazine (4.54 g, 16.9 mmol), tetrakis (triphenylphosphine) palladium (0) (1.6 g, 1.41 mmol), potassium carbonate ( 3.9 g, 28.2 mmol) and 1,4-dioxane/water (80 ml/28.2 ml) mixture was refluxed at 120° C. for 4 hours.After filtering at 60°C, it was washed with 1,4-dioxane, distilled water, and MeOH at 60°C to obtain compound 129 (H) (5.4 g, 68%).
65 %
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃;
3 Preparation of compound 2-129
9-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-3-yl)-9H-carbazole (6.5 g, 14.1 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (4.54 g, 16.9 mmol), tetrakis(triphenylphosphine)palladium(0) (1. 6 g, 1.41 mmol), potassium carbonate (3.9 g, 28.2 mmol), and a mixture of 1,4-dioxane/water (80 mL/28.2 mL) were refluxed in a round-bottomed flask at 120°C for 4 hours. Thereafter, the mixture was filtered at 120° C., and then washed with 1,4-dioxane, distilled water, and methanol (MeOH) to obtain compound 2-129(F) (5.4 g, 68%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 120℃; for 12h;
Add 100mmol of 1-(4-bromobenzene)-2-phenyl 1H-benzo[d]imidazole, 100mmol of M5, 41.4g of potassium carbonate (300mmol), 800ml of THF and 200ml of water into the reaction flask, and add 1mol% of Pd(PPh3)4. React at 120°C for 12h. After the completion of the reaction, the reaction was stopped, and the reactant was cooled to room temperature, water was added, and the organic phase was concentrated to obtain a white solid, filtered and washed with water, and the obtained solid was purified by recrystallization with toluene to obtain a white powder M6. Among them, the amount of Pd(PPh3)4 added is 1 mol% of M5.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 120℃; for 3h;
6 Preparation of compound 1
General procedure: One neck round bottom flask (One neck r.b.f)9-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]furan-4-yl)-9H-carbazole(12.5 g, 27.2 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (8.74 g, 32.6 mmol), tetrakis (triphenylphosphine) palladium (0) (3.1 g) , 2.72 mmol), potassium carbonate (7.5 g, 54.5 mmol), and 1,4-dioxane/water (150 ml/30 ml) mixture was refluxed at 120° C. for 3 hours. After filtering at 120°C, it was washed with 1,4-dioxane, distilled water, and MeOH at 120°C.Washed to obtain compound 1 (C) (11.2 g, over two step 71%)
With 18-crown-6 ether; copper; potassium carbonate In 1,2-dichloro-benzene at 180℃; for 48h; Inert atmosphere;
4
The organic compound of [Formula 4] was synthesized through the following reaction scheme.Add dichlorobenzene (50 mL) to a 100 mL two-necked round-bottom flask and poise with dry nitrogen. The intermediate (j) (2.4 g, 3.9 mmol), 1- (4-bromophenyl) -2-phenyl-1H-benzo [d] imidazole (1.4 g, 4.7 mmol), Cu powder (0.44 g, 7.0 mmol), Potassium carbonate (2.2g, 15.6mmol) and 18-crown-6 (0.21g, 0.78mmol) were added and refluxed at 180°C for 48 hours. After completion of the reaction, extraction is performed with water and MC. After removing the residual moisture with MgSO4, it is purified by column chromatography using EA:Hex to obtain an organic compound of the following [Formula 4] (yield: 33%).
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In 5,5-dimethyl-1,3-cyclohexadiene for 12h; Reflux;
1 Comparative Synthesis Example 1: Synthesis of Compound Z-1
Combine 1eq (10g) of 1-(4-bromophenyl)-2-phenylbenzimidazole and 1eq (9g) of bis(4-benzidine) with 2eq (5.5g) of sodium tert-butoxide and 0.03eq (0.8 g) of Pd2(dba)3 was suspended in 120 mL of xylene, 0.09 eq of tri-tert-butyl phosphine was added thereto, and then refluxed and stirred for 12 hours.When the reaction was completed, the organic layer therefrom was extracted with xylene and distilled water, dried with magnesium sulfate, and filtered, and the filtrate was concentrated under reduced pressure. After removing the organic solvent, the residue was treated with hexane:dichloromethane=8:2 (v/v) through a silica gel column, and the solid thus obtained was recrystallized with dichloromethane and hexane to obtain 12.2 g (Y = 72%) of compound Z-1.
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In ethanol; lithium hydroxide monohydrate; toluene for 8h; Inert atmosphere; Reflux;
1.14 (14) Synthesis of compound 25
In a three-necked flask, add 5g of intermediate,5.8g compound 25-1, 4.2g potassium carbonate,60ml toluene, 20ml ethanol and 10ml water,Replace the air in the system with nitrogen,Under nitrogen protection, 0.26 g of tetrakis(triphenylphosphine) palladium was added,Heated to reflux for 8 hours,After TLC monitoring the complete reaction of the raw material, it was cooled down,The reaction solution was washed with water until neutral, dried over anhydrous sodium sulfate, and then purified by silica gel column. The obtained product was recrystallized from toluene to obtain 6.1 g of compound 25 with a yield of 72.6%.
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 3h;
8 Preparation of Compound 1
General procedure: To Compound 1-6 (12.3 g, 24.2 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (6.5 g, 1 eq.), Pd(PPh3)4 (1.4 g, 0.05 eq.), K2CO3 (10.0 g, 3.0 eq.) and 1,4-dioxane/H2O were added, and the mixture was stirred for 3 hours at 110° C. After the reaction was completed, the result was cooled to room temperature, and produced solids were filtered to obtain target Compound 1 (12.2 g, 82%).
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 3h;
34 Preparation of Compound 148
General procedure: To Compound 148-6 (11.1 g, 21.8 mmol), 2-chloro-4,6-diphenyl-1,3,5-triazine (7.1 g, 1 eq.), Pd(PPh3)4 (1.5 g, 0.05 eq.), K2CO3 (10.5 g, 3.0 eq.) and 1,4-dioxane/H2O were added, and the mixture was stirred for 3 hours at 110° C. After the reaction was completed, the result was cooled to room temperature, and produced solids were filtered to obtain target Compound 148 (12.3 g, 82%).
Stage #1: 1-(4-bromophenyl)-2-phenyl-1H-benzo[d]imidazole; C34H30BNO2 With potassium carbonate In ethanol; water; toluene Inert atmosphere;
Stage #2: With palladium diacetate; XPhos In ethanol; water; toluene Reflux; Inert atmosphere;
2.2 2.1 Synthesis of compound A1
General procedure: In a 250mL reaction bottle, add intermediate MA (15.52g, 33mmol), 4-chloro-2,6-diphenylpyridine (7.95g, 30mmol), potassium carbonate (12.44g, 90mmol), toluene (120mL), ethanol (45mL), water (45mL), nitrogen filling and stirring for 15min, then palladium acetate (0.067g), X-Phos (0.286g), heating and reflux for 5 hours. At the end of the reaction, extraction, the organic phase was taken for silica gel short column chromatographic filtration, the filtrate was vacuum evaporated to remove the solvent, and the crude product was recrystallized with toluene/ethanol, and filtered to obtain 12.8g of compound A1, which was a white solid powder with a yield of 74.4%, a purity of 99.89%, and a purity of 99.92% after a sublimation.
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