2-(3-Bromophenyl)-4,6-diphenyl-1,3,5-triazine

white powder

Under a nitrogen atmosphere, 50g (187mmol) the compound 2-chloro-4, 6-diphenyl-1, 3, 5-triazine was dissolved in 1L of tetrahydrofuran (tetrahydrofuran, THF) added thereto 45g (224.12mmol) (3-bromophenyl) borate, and 2.1g (1.87 mmol) of tetrakis (triphenylphosphine) palladium, and the mixture was stirred. Subsequently, thereto added 64g (467mmol) of potassium carbonate saturated aqueous solution, and the resulting mixture was heated at reflux for 80 12 hours. When the reaction is complete, add water to the reaction solution, and the mixture was extracted with dichloromethane (dichloromethane, DCM), followed by removal of water with anhydrous MgSO4 filtered and concentrated under reduced pressure. Subsequently, the obtained residue was separated and purified via flash column chromatography to give 69g (95percent) compound II-1.SYNTHESIS EXAMPLE 1 Synthesis of Intermediate I-1 (0197) (0198) The compound, 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (50 g, 187 mmol) was dissolved in 1 L of THF (tetrahydrofuran) in a nitrogen environment, (3-bromophenyl)boronic acid (45 g, 224.12 mmol) and tetrakis(triphenylphosphine)palladium (2.1 g, 1.87 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (64 g, 467 mmol) was added thereto, and the resulting mixture was heated and refluxed at 80° C. for 12 hours. When the reaction was complete, water was added to the reaction solution. dichloromethane (DCM) was used for an extraction, and an extract therefrom was filtered after removing moisture with anhydrous MgSOIn a nitrogen environment, 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (50 g, 187 mmol) was dissolved in 1 L of tetrahydrofuran (THF)To this was added (3-bromophenyl) boronic acid (45 g, 224.12 mmol)And tetrakis (triphenylphosphine) palladium(2.1 g, 1.87 mmol) were added and stirred. Saturated water-saturated potassium carbonate (64 g, 467 mmol)And the mixture was refluxed by heating at 80 ° C for 12 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM). Then, water was removed with anhydrous MgSO 4, Filtered and concentrated under reduced pressure.The thus-obtained residue was purified by flash column chromatography(Flash column chromatography) to obtain intermediate II-1(69 g, 95percent).Synthesis Synthesis of Intermediate I-1 (0132) (0133) The compound, 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (50 g, 187 mmol, TCI Inc.) was dissolved in THF (1 L) under a nitrogen environment, (3-bromophenyl)boronic acid (45 g, 224.12 mmol, TCI Inc.) and tetrakis(triphenylphosphine)palladium (2.1 g, 1.87 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (64 g, 467 mmol) was added thereto, and the obtained mixture was heated and refluxed at 80° C. for 12 hours. When the reaction was complete, water was added to the reaction solution, and the mixture was extracted with dichloromethane (DCM), filtered after removing moisture with anhydrous MgSOSynthesis Synthesis of Intermediate I-1 A compound, 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (50 g, 187 mmol, TCI) was dissolved in THF (1 L) under a nitrogen environment, (3-bromophenyl)boronic acid (45 g, 224.12 mmol) and tetrakis(triphenylphosphine)palladium (2.1 g, 1.87 mmol) were added thereto, and the mixture was stirred. Potassium carbonate saturated in water (64 g, 467 mmol) was added thereto, and the obtained mixture was heated and refluxed at 80° C. for 12 hours. When the reaction was complete, water was added to the reaction solution, and the mixture was extracted with dichloromethane (DCM) and then, filtered after removing moisture with anhydrous MgSOThe compound 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (5.35 g, 20 mmol) and 3-bromo-phenylboronic acid (4.01 g, 20 mmol) were dissolved in toluene (100 ml).Add ethanol (20 ml) and aqueous potassium carbonate (2M, 20 ml).In the N2 atmosphere, Tetrakis(triphenylphosphine)palladium (345 mg, 0.3 mmol) was added and the reaction was stirred at 90 ° C for 12 hours;After the reaction is completed, distilled water is added to the reaction mixture to separate the toluene layer.Extract the water layer with dichloromethane, The extracted organic layer was dried over anhydrous magnesium sulfate and filtered.The dichloromethane was distilled off under reduced pressure, and the obtained crude product was separated by column chromatography.The eluent is petroleum ether, which gives a white solid (compound 1).The yield was 75.3percent (5.84 g).The compound 2-chloro-4, 6-diphenyl-1, 3, 5-triazine (72 g, 268 mmol) was dissolved in 1 L of THF in a nitrogen atmosphere, 3-bromophenyl boronic acid (45 g, 224.12 mmol) and tetrakis (triphenylphosphine) palladium (2.63 g, 2.82 mmol) were added and stirred. Saturated water-saturated potassuim carbonate (51.6 g, 373.54 mmol) was added and heated at 80 ° C for 53& Lt; / RTI & gt; for a period of time. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with dichloromethane (DCM)The water was removed with MgSO4, filtered and concentrated under reduced pressure. The residue thus obtained was purified by flash column chromatographySeparation and purification were conducted to obtain the above compound I-5 (57 g, 66percent).Compound 10-1 (1.5 g, 5.9 mmol), benzamidine hydrochloride (2.0 g, 13.0 mmol) and NaOH (0.5 g, 13.0 mmol) were added to ethanol (20 ml) and refluxed for 12 hours.Washed with water and ethanol to obtain Compound 10-2 (1.7 g, 74percent).Subsequently, under an argon gas atmosphere, the intermediate body 5-1 (130g, 50 mmol), benzamidine hydrochloride (152g, 100 mmol), anhydrous ethanol (1 L), and sodium hydroxide (42 g) were added together in sequential order, and stirred at 80 degrees C for 16 hours. Subsequently, sodium-t-butoxide (20 g, 208 mmol) were further added and heated at 80 degrees C for 16 hours with stirring. After the reaction solution was cooled down, a solid was separated by filtration and washed with methanol to obtain an intermediate body 5-2 (67g, a yield of 37percent).Subsequently, under an argon gas atmosphere, the intermediate body 1C-1 (130 g, 50 mmol), benzamidine hydrochloride (152 g, 100 mmol), anhydrous ethanol (1 L), and sodium hydroxide (42 g) were added together in sequential order, and stirred at 80 degrees C. for 16 hours. Subsequently, sodium-t-butoxide (20 g, 208 mmol) were further added and heated at 80 degrees C. for 16 hours with stirring. After the reaction solution was cooled down, a solid was separated by filtration and washed with methanol to obtain an intermediate body 1H-2 (67 g, a yield of 37percent).Into a 1 L four-necked round bottom flask equipped with a stirrer, an Erlin condenser, a nitrogen inlet tube and a thermometer were placed 74.8 g (0.268 mol) of the benzenamine obtained in the above , 84.6 g of benzamidine hydrochloride (0.54 mol) of sodium hydroxide, 22.7 g (0.57 mol) of sodium hydroxide and 500 mL of ethanol, and the mixture was allowed to react at a reflux temperature of ethanol for 18 hours under a nitrogen stream. After cooling to room temperature, 10.8 g (0.112 mol) of sodium tert-butylate was added, and the mixture was reacted again under a nitrogen stream at the reflux temperature of ethanol for 16 hours.The resulting reaction solution was cooled to room temperature, and the precipitated crystals were suction filtered. Next, the crystals remaining in the Nutsche were thoroughly washed with ethanol and water to obtain 28.0 g of a white target compound (yield: 26.7percent).100mlThree mouthfulsIn the bottleM-bromobenzaldehyde(10.8mmol, 2g), Benzoquinone hydrochloride(21.6mmol, 3.8g), Na2CO3 (21.6 mmol, 2.2 g), Ni(OAc) 2 (1.08 mmol, 0.27 g), The molar ratio is charged at 1:2:2:0.1.The solvent was chosen to be 50 g of toluene.The reaction was controlled to stir at 110 ° C for 30 h.filter, Washed, Recrystallization from absolute ethanol, The obtained cake was vacuum dried to obtain a product of 3.6 g.The yield was 83percent.General procedure: A mixture ofaldehyde 1 (6.8 mmol), amidine hydrochloride 2 (2 g, 11.4 mmol), Na2CO3 (1.21 g, 11.4 mmol, 1.0 equiv) andCu(OAc)2 (10 molpercent) was stirred in toluene (20 mL) under100 °C in air for 24 h. After completion of the reaction, themixture was cooled to room temperature. The water wasadded to the reaction system and atmospheric distillation untiltoluene was evaporated. The resulting solution was filteredand residue with hot water washed 3 times. The crude productwas purified by column chromatography on silica gel usingpetroleum ether/EtOAc (100:1) as an eluent to give the correspondingproducts 7a-7x.(1) 1, 3-Dibromobenzene 28 g(0.119 mol) was dissolved in THF 600 mL, and then n-BuLi 47.5 mL was slowly added dropwise thereto at -78°C, followed by stirring for 1 hour. 2-Chloro-4, 6-diphenyl-1, 3, 5-triazine 47.5 mL was slowly added dropwise thereto, and the resultant mixture was stirred at room temperature for 5 hours after the temperature was slowly raised. After the reaction is completed, extraction with EA and distilled water and column separation were sequentially performed, thereby obtaining Compound 9-1 15.7 g (40.43 mmol, 40.4percent).1, 3-dibromobenzene was dissolved in THF and cooled into the temperature of —78° C. n-l3uLi (60 mE, 2.5M) was slowly dropped into the solution, and 2-chioro-4, 6-diphenyl-1, 3, 5-triazine (40 g, 149.7 mmol), whichdissolved in THF, was slowly dropped. The solution was slowly heated up to the room temperature and stirred forhours. After completion of the reaction, the resultant was re-precipitated by THF/MeOH and MC (methylenechloride)/hexane such that 2-(3-bromophenyl)-4, 6-diphenyl-15-triazine (16 g, yield: 28percent) was obtained.Under an argon stream, benzamidine hydrochloride (470 mg, 3.0 mmol) was suspended in xylene (7.5 mL).The suspension was cooled to 0 ° C., triethylamine (420 μL, 3.0 mmol) and 3-bromobenzoyl chloride (130 μL, 1.0 mmol) were added, and the mixture was stirred at 0 ° C. for 30 minutes and further at 60 ° C. for 3 hours.After allowing to cool, 1, 1, 3, 3-tetramethyldisilazane (520 μL, 3.0 mmol) was added to the reaction mixture, and the mixture was stirred at 150 ° C. for 5 hours.After standing to cool, the low boiling fraction was distilled off under reduced pressure from the reaction mixture, water was added to the obtained residue, and the solid was filtered off.The solid was washed with water, methanol, then hexane.The obtained solid was dried under reduced pressure to obtain the objective 2- (3-bromophenyl) -4, 6-diphenyl-1, 3, 5-triazine as a white solid (278 mg, 72percent).2.1Weigh 3.7 g of m-bromobenzaldehyde 7.7 g, Benzamidine hydrochloride0.405 g CuCl26.36g of sodium carbonate is dissolved in 60mL of toluene, the temperature is set to 130 ° C, the reaction is turned on;2.2After the reaction was completed, after cooling to room temperature, the cake was plated with silica gel and diatomaceous earth, and the reaction mixture was filtered.Concentrate the reaction to give a brown solid, then at room temperatureBeating with petroleum ether to an off-white solid 4.1g, yield 52percent, HPLC = 99percent;To a round bottom flask, 1-bromo-3-iodo-benzene (60.0 g, 212 mmol), 480 mL of tetrahydrofuran were added and the temperature falls to -78° C under a nitrogen condition . After 30 minutes, 126 mL of 1.6 M n-butyllithium (202 mmol) was slowly added dropwise . After 1 hour, 2-chloro-4, 6-diphenyl-1, 3, 5-triazine 62.4 g (233 mmol) was dissolved in 250 mL of tetrahydrofuran, after dropping a solution slowly comes to room temperature and then stirred for 30 minutes. After stirring for about 1 hour at room temperature, 2N hydrochloric acid was added dropwise to the reaction solution until the acid is an aqueous solution. The combined organic layer was then extracted, concentrated and then separated by column chromatography to give <4-a> 24.7g (yield 30percent).To a 1000 ml flask was added 30.0 g (83.51 mmol) of Intermediate L-1, 28.35 g (100.21 mmol) of 1-bromo-3-iodebenzene, 23.08 g (167.02 mmol) of potassium carbonate, Tetrakis (triphenylphosphine) palladium )) 4.83 g (4.18 mmol) in tetrahydrofuran(350 mL) and water (100 mL), and the mixture was heated under reflux in a nitrogen stream for 10 hours. The resultant mixture was added to 1500 mL of methanol and the crystallized solid was filtered, and then dichloromethane was added thereto. The resulting mixture was filtered through silica gel / celite, and the organic solvent was removed in an appropriate amount, and the filtrate was recrystallized from methanol to obtain 37.3 g of 83percent Yield).

Molecular Weight:388.3
XLogP3:5.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:387.03711
Monoisotopic Mass:387.03711
Topological Polar Surface Area:38.7
Heavy Atom Count:25
Complexity:380
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes