With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
Synthesis Example 32: Synthesis of Intermediate I-32 The compound, 2-chloro-4,6-diphenyl-1,3,5-triazine (50 g, 187 mmol) was dissolved in THF (1 L) under a nitrogen environment, (4-bromophenyl)boronic acid (45 g, 224.12 mmol, Aldrich Corporation), 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 MgSO4 and concentrated under a reduced pressure. This obtained residue was separated and purified through flash column chromatography to obtain Compound I-32 (70 g and 96percent). HRMS (70 eV, EI+): m/z calcd for C21H14BrN3: 387.0371. found: 387. Elemental Analysis: C, 65percent; H, 4percent
60%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 100℃; for 12 h;
2-chloro-4,6-diphenyl-1,3,5-triazine (20g, 1.0eq), (4- bromophenyl) boronic acid (16.5g, 1.1eq), K2CO3 (20.6g, 2.0eq), Pd (PPh3) 4 (8.6g, 0.1eq) in toluene 400 ml / 100 ml of ethanol / 50 ml H2O for 12 hours in a mixture of 100 It was stirred. And extracted with MC MC: hexane = 1: 3 to the separation column to obtain a white solid compound 72-1. (4.5g, 60percent)
60%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 53 h; Inert atmosphere
The compound 2-chloro-4,6-diphenyl-1,3,5-triazine (72 g, 268 mmol) was dissolved in THF (tetrahydrofuran)(4-bromophenyl) boronic acid (45 g, 224.12 mmol) andTetrakis (triphenylphosphine) palladium (2.63 g, 2.82 mmol) was added and stirred. Saturated potassuim in waterCarbonitrile (51.6 g, 373.54 mmol), and the mixture was refluxed by heating at 80 for 53 hours. After completion of the reaction,Water was added, and the mixture was extracted with dichloromethane (DCM). Then, water was removed with anhydrous MgSO 4, filtered, and concentrated under reduced pressure. thisThe residue thus obtained was separated and purified by flash column chromatography to obtain Compound I-4 (62 g, 60percent).
30%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 60℃; for 18 h; Inert atmosphere
Compound in a nitrogen stream to a flask 1L reaction [259-1] 40g (0.15mol), compound [241-6] 36.1g (0.18mol), potassium carbonateDissolve 41.4g (0.30mol) in 1,4-dioxane and 410mL, 180 mL of purified water and then put the temperature was raised to tetrakis (updated in about 60 Lee thereby phenyl phosphine) palladium added 5.2g (4.5mmol) and stirred under reflux for 18 hours. After completion of the reaction slowly to room temperature and coldSerious filtered and then the reaction solution. The filtered solid is extracted with dichloromethane, and saturated brine. The organic layer was separated, anhydrousDried with magnesium sulfate, filtered and concentrated under reduced pressure. Using the concentrate was purified by column chromatography method, to obtain the intermediate compound to prepare a [259-2] 17g (30percent).
Reference：
[1] Patent: US2017/331067, 2017, A1, . Location in patent: Paragraph 0260-0263
[2] Chemistry - An Asian Journal, 2016, vol. 11, # 6, p. 868 - 873
[3] Patent: KR2015/75169, 2015, A, . Location in patent: Paragraph 0206-0209
[4] Patent: KR2015/59395, 2015, A, . Location in patent: Paragraph 0162; 0163; 0164; 0165
[5] Patent: KR2015/88163, 2015, A, . Location in patent: Paragraph 0342-0345
2
[ 3842-55-5 ]
[ 68716-49-4 ]
[ 23449-08-3 ]
Yield
Reaction Conditions
Operation in experiment
66%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 70℃; for 5 h;
2.68 g (10 mmol) of 2-chloro-4,6-diphenyl-1,3,5-triazine(2-chloro-4,6-diphenyl-[1,3,5]-triazine),2.82 g (10.0 mmol) of 4-bromo-phenylboronic acid pinacol ester(4-bromo-phenylboronic acid pinacol ester),0.58 g (0.5 mmol) of Pd(PPh3)4 and 4.14 g (30.0 mmol) ofK2CO3 was dissolved in 60 mL of a mixture of THF and H2O (2:1 by volume) to obtain a solution which was then stirred at 70C for about 5 hours.And then extracted three times with 60 mL of water and 60 mL of diethyl ether.The organic layer was collected and dried over magnesium sulfate to evaporate the solvent.The residue was separated and purified by silica gel column chromatography to obtain 2.56 of Intermediate I-7(yield: 66percent).
Reference：
[1] Patent: WO2006/67931, 2006, A1, . Location in patent: Page/Page column 60
[2] Patent: EP2808323, 2014, A1,
[3] Patent: CN107880030, 2018, A,
[4] Patent: CN108440430, 2018, A,
4
[ 106-37-6 ]
[ 3842-55-5 ]
[ 23449-08-3 ]
Reference：
[1] Chemical Communications, 2016, vol. 52, # 73, p. 10956 - 10959
5
[ 3842-55-5 ]
[ 1073062-59-5 ]
Reference：
[1] Patent: JP2017/197482, 2017, A, . Location in patent: Paragraph 0204
6
[ 3842-55-5 ]
[ 89598-96-9 ]
[ 864377-31-1 ]
Yield
Reaction Conditions
Operation in experiment
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
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.
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
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 MgSO4 and then, concentrated under a reduced pressure. This obtained residue was separated and purified through flash column chromatography to obtain the intermediate I-1 (69 g and 95percent). (0199) HRMS (70 eV, EI+): m/z calcd for C21H14BrN3:387.0371, found: 387. (0200) Elemental Analysis: C, 65percent; H, 4percent
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
In 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).
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
Synthesis Example 1: 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 MgSO4, and concentrated under a reduced pressure. The obtained residue was separated and purified through column chromatography to obtain Intermediate I-1 (69 g and 95percent). (0134) FIRMS (70 eV, EI+): m/z calcd for C21H14BrN3: 387.0371. found: 387. (0135) Elemental Analysis: C, 65percent; H, 4percent
95%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h; Inert atmosphere
Synthesis Example 1: 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 MgSO4 and concentrated under a reduced pressure. The obtained residue was separated and purified through column chromatography to obtain Compound I-1 (69 g, 95percent). HRMS (70 eV, EI+): m/z calcd for C21H14BrN3: 387.0371. found: 387. Elemental Analysis: C, 65percent; H, 4percent
75.3%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 90℃; for 12 h; Inert atmosphere
The 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).
66%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 53 h; Inert atmosphere
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).
Reference：
[1] Patent: CN105566200, 2016, A, . Location in patent: Paragraph 0326; 0327; 0328; 0329
[2] Patent: US2017/84845, 2017, A1, . Location in patent: Paragraph 0197-0200
[3] Patent: KR2017/11338, 2017, A, . Location in patent: Paragraph 0390; 0392-0395
[4] Patent: US2017/222158, 2017, A1, . Location in patent: Paragraph 0132; 0133; 0134; 0135
[5] Patent: US2017/331067, 2017, A1, . Location in patent: Paragraph 0184-0187
[6] Patent: CN108409730, 2018, A, . Location in patent: Paragraph 0054; 0058; 0059; 0060
[7] Patent: KR2015/59395, 2015, A, . Location in patent: Paragraph 0168; 0169; 0170; 0171
7
[ 108-36-1 ]
[ 3842-55-5 ]
[ 864377-31-1 ]
Yield
Reaction Conditions
Operation in experiment
40.4%
Stage #1: With n-butyllithium In tetrahydrofuran-d8 at -78℃; for 1 h; Stage #2: at 20℃; for 5 h;
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).
28%
With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 12 h;
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.
Reference：
[1] Patent: EP2857395, 2015, A1, . Location in patent: Paragraph 0076
[2] Patent: US2018/130953, 2018, A1, . Location in patent: Paragraph 0211; 0212
[3] Patent: JP2016/108255, 2016, A, . Location in patent: Paragraph 0087-0089
8
[ 591-18-4 ]
[ 3842-55-5 ]
[ 864377-31-1 ]
Yield
Reaction Conditions
Operation in experiment
30%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h; Inert atmosphere Stage #2: at 20℃; for 1.5 h; Inert atmosphere
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).
Next, 4.36 g (100.0 mmoles) of a 55percent dispersion of sodium hydride and 70 ml of dehydrated DMF were placed in a 2000-ml three-necked flask and the mixture was stirred in a stream of nitrogen. To this mixture was added dropwise a solution of 10.4 g (40.6 mmoles) of the aforementioned solid C in 150 ml of dehydrated DMF over 10 minutes. Upon completion of the dropwise addition, the mixture was stirred continuously for 1 hour. Then, to the mixture was added dropwise a solution of 20.9 g (78.0 mmoles) of 2-chloro-4,6-diphenyl-1,3,5-triazine in 300 ml of dehydrated over 1 hour. Upon completion of the dropwise addition, the mixture was stirred continuously for 3 hours. Thereafter, 900 g of water was added, the crystals separated were collected by filtration, reslurried twice with 450 g of water, further reslurried with 450 g of methanol, the solvent was distilled off under reduced pressure, and 42.0 g of brown crystals was obtained. The brown crystals were purified by crystallization from THF and methanol and stripped of the solvent under reduced pressure to give 13.4 g (18.6 mmoles, 46percent yield) of a light brown solid or Compound 114: APCI-MS, m/z 719 [M+1]+; melting point, 498°C.
Synthesis of Comparative Compound 1. 3,6-Diphenyl-9H-carbazole (4.00 g, 12.52 mmol) was dissolved in anhydrous DMF (170 mL) and treated with NaH (0.751 g, 18.79 mmol, 60percent dispersion in mineral oil) while stirring vigorously at room temperature providing yellow solution. Once H2 evolution stopped, the solution was stirred for 1 hour, and then treated with 2-chloro-4,6-diphenyl-1,3,5-triazine (5.03 g, 18.79 mmol), and left stirred overnight at room temperature. After stirring for ?30 minutes, reaction solution had significant white precipitate swirling around. The crude mixture was quenched with water and filtered. The white precipitate was washed with water, MeOH, and EtOH. The material was recrystallized from toluene (400 mL) to obtain the target, Comparative Compound 1 with 99.86percent purity. One more recrystallization from toluene gave a purity of 100percent to afford 6.0 g (87percent yield).
Prepare the format reagent, 2.67g of 2-chloro-4,6-diphenyl-1,3,5-triazine,0.4 mol of magnesium was added to 50 tetrahydrofuran, and the temperature was raised to reflux reaction.Gradually adding the remaining 24gA saturated solution of 2-chloro-4,6-diphenyl-1,3,5-triazine in tetrahydrofuran was kept at reflux for about 1 h, and was used.Add 29.6 g of 1-bromo-3-iodo-2-toluene and 300 ml of tetrahydrofuran to another three-necked flask and mix well.Nitrogen protection, cooling to -5 C, transfer the prepared format reagent to the dropping funnel,Slowly add dropwise to keep the temperature of the system not exceeding 10 C.After the addition was completed, stir for 30 minutes and then slowly increase to room temperature.After 5 hours, the reaction of the starting material was completed, and a saturated aqueous solution of ammonium chloride was added dropwise to the reaction solution.After stirring for 5 min, dichloromethane was extracted, and the organic phase was dried under reduced pressure.The residue was subjected to column chromatography to give 25.7 g of Intermediate 39-1. (yield 64%)
2,4-diphenyl-6-(thianthren-1-yl)-1,3,5-triazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; at 110℃; for 18h;Inert atmosphere;
The specific reaction steps are as follows:Thianthrene-1-boronic acid (3.84mmol, 1.00g),2-Chloro-4,6-diphenyl-1,3,5-triazine (4.22 mmol, 1.13 g),Potassium phosphate (19.20 mmol, 4.07 g), tricyclohexylphosphine (0.31 mmol, 86 mg), Pd2 (dba) 3 (0.192 mmol,176 mg), 1,4-dioxane 100 mL was sequentially added to the reactor, and after passing nitrogen for 15 minutes,The reaction was heated at 110 C for 18 h. After the reaction is over, the system is returned to room temperature.The organic phase was extracted with dichloromethane and brine, and the solvent was evaporated under reduced pressure.The crude product was separated and purified by column chromatography. The eluent was petroleum ether/dichloromethane 5:1.The product of structure 1 was obtained in a yield of 67%. Structure 1 formula: C27H17N3S2;
2,4-diphenyl-6-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)-1,3,5-triazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;
Sub 1-I-22 (17.0 g, 63.5 mmol), 1,3-bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzene (16.77 g, 50.8 mmol) , K2CO3 (26.33 g, 190.5 mmol) and Pd (PPh3) 4 (3.67 g, 3.2 mmol) were added to a round-bottomed flask and dissolved in THF (190 mL) and water (95 mL) for 12 hours at 80 C. It was refluxed. After the reaction was completed, the reaction was cooled to room temperature, extracted with CH2Cl2, and washed with water. The organic layer was dried over MgSO 4, concentrated, and the resulting organic was separated using a silica gel column to give Sub 1-22 (23.5 g, 85%).
5-(4,6-diphenyl-1,3,5-triazin-2-yl)-2-fluorobenzonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 60℃; for 3h;
30 g (181.9 mmol) of (3-cyano-4-fluorophenyl) boronic acid,2-chloro-4,6-diphenyl-1,3,5-triazine (181.9 mmol),Mix 200 mL of tetrahydrofuran and 100 mL of water,Heat to 60 C.Potassium carbonate (545.6 mmol)And tetrakistriphenylphosphinepalladium (1 mmol)Was added and stirred for 3 hours in a reflux state.After the reaction, the reaction solution returned to room temperature was filtered to obtain a solid, and this solid was recrystallized twice with tetrahydrofuran / ethanol,57.6 g of compound 1-A was obtained (yield 90%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
88K+ Compounds
Competitive Price
1-2 Day Shipping
