2-Chloro-4,6-diphenylpyrimidine

white solid

2-chloro-4,6-diphenylpyrimidine is a member of pyrimidines.

Preparation of Compound 1-10 [113] 2, 4, 6-trichloropyrimidine (20 g, 0.109 mol), phenylboronic acid (29.2 g, 0.239 mol), Pd(PPhIn a 500 mL three-necked flask under argon atmosphere, 2, 4, 6-trichloropyrimidine (5 g, 27.3 mmol), phenylboronic acid (6.7 g, 54.9 mmol), tetrakistriphenylphosphine palladium (1.26 g, 1.09 mmol ), Dimethoxyethane (DME, 100 mL) and a 2M sodium carbonate aqueous solution (82 mL, 164 mmol) were added, and the mixture was reacted for 8 hours while heating and refluxing. After the reaction solution was cooled to room temperature, the aqueous layer was separated and the organic layer was dried over magnesium sulfate. The insoluble material was removed by filtration, and the organic solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain intermediate (a) (5.6 g, yield 76.9percent).Take 5000ml three necked flask, equipped with mechanical stirrer, condenser. Feed: 18.2 g of 2, 4, 6-trichloropyrimidine (molecular weight 182, 0.10 mol), phenylboronic acid 28.1 g (molecular weight 122, 0.23 mol), tetrakis(triphenylphosphine)palladium 12.0g (0.0104mol), potassium carbonate 60 g (0.435 mol), tetrahydrofuran 600 ml, toluene 400 ml, water 400 ml. Mechanical agitation was initiated under conditions of reduced pressure ventilation Ar gas three times to maintain protection, monitoring the reaction by TLC (thin layer chromatography), refluxed for 8 hours, the reaction was complete. Allowed to cool, the reaction system was divided into two layers, the organic layer was separated and evaporated to dryness to give a solid product, which was recrystallized from toluene to give intermediate M3-1 was 19.9 g, molecular weight 266, 75percent yield.Under the protection of Ar gas, in 500mL three-neck bottle added 2, 4, 6- Trichloropyrimidine18.2g(molecular weight 182, 0.10mol), Benzene boronic acid 28. 1g (molecularweight 122, 0 · 23 mol), Tetrakis (triphenylphosphine) palladium12.0g(0.0104mol), 600ml of THF, 400mL toluene, Potassium carbonate 60g (0 · 435mol) was dissolved in 400ml water and the formation of solution was added intoreaction flask. After repeated ventilation under reduced pressure, startelectric mixer, the reaction was monitored by TLC (thin layer chromatography), after at reflux for 8h and the reaction was complete. Allowed to cool, thereaction system was divided into two layers, the organic layer was separatedand evaporated to dryness to give a solid product, it was recrystallized using toluene to give 19.9gof intermediate molecular weight of 266, yield of 75percent.Under Ar protection, in a 5000ml three-necked flask was added 2, 4, 6_ trichloropyrimidine 18.2g (molecular weight 182, 0.1Omol), benzene boronic acid 28.1g (molecular weight 122, 0.23mol ), tetrakis (triphenylphosphine) palladium 12.0g (0.0104mol), 600ml ^ THF, 400ml of toluene, potassium carbonate 60g (0.435mol) dissolved in 400ml of water was added to the reaction flask.After refluxed for 8 hours, repeated under reduced pressure ventilation, electric start stirring, the reaction was monitored by TLC (thin layer chromatography), the reaction was complete.Allowed to cool, the reaction system was divided into the second floor, and the organic layer was separated, evaporated to dryness, to obtain a solid product, which was recrystallized from toluene to give 19.9g of intermediate molecular weight 266, 75percent yield.M2-1: under Ar protection, a 5000ml three-necked flask were added 18.2 g of 2, 4, 6-trichloropyrimidine (molecular weight 182, 0.10mol), phenylboronic acid 28.1 g (molecular weight 122, 0.23mol), four (triphenylphosphine) palladium 12.0g (0.0104mol), 600ml of THF to, toluene 400ml, potassium carbonate 60g (0.435mol) dissolved in 400ml of water was added to form a reaction flask. After repeated under reduced pressure ventilation, electric start stirring, the reaction was monitored by TLC (thin layer chromatography), refluxed for 8 hours, the reaction was complete. Allowed to cool, the reaction system for the sub-floor, the organic layer was separated, evaporated to dryness to give a solid product, recrystallised from toluene to give 19.9g intermediate molecular weight 266, 75percent yield.Take 5000ml three bottles, with mechanical mixing, condenser. Feeding: 2, 4.6-trichloropyrimidine (molecular weight: 182, 010 mol), 28.1 g of benzene boronic acid (molecular weight: 122, 0.23 mol), 12.0 g (0.0104 mol) of tetraphenylphenylphosphine, 60 g of potassium carbonate (0.435 mol ), Tetrahydrofuran 600ml, toluene 400ml, water 400ml. start mechanical agitation, Under the conditions of reduced pressure ventilation 3 times to maintain Ar gas protection, with TLC (thin layer chromatography) to monitor the reaction, After 8 hours of reflux, the reaction was complete. Let cool, the reaction body divided into two layers, separated from the organic layer, evaporated, The solid product was obtained and recrystallized from toluene to give 19.9 g of intermediate M2-1, molecule The amount of 266, the yield of 75percent.A mixture of 2, 4, 6-trichloropyrimidine (PYR, 1.3 ml, 7 mmol), phenylboronic acid (Ph-BoA, 1.5 g, 12 mmol), Pd(PPh3P)4 (0.2 g, 0.17 mmol), 40 ml of 2M aqueous K2CO3 solution, 40 ml of water, 25 mlof ethanol, and 80 ml of toluene were added in a two neck round bottom flask equipped with condenser and refluxed at 110 °C for 8 h under nitrogen atmosphere. After completion of the reaction, the mixture was worked up using ethyl acetate (60 ml) and water (50 ml). The organic layer was dried over anhydrous magnesium sulfate and then filtered and concentrated. The crude residues were separated using asilica column and an n-hexane: dichloromethane (4:1) solvent system toobtain the intermediate 2P-PYR as a white solid. 2.3.2.1. 2-Chloro-4, 6-diphenylpyrimidine. Yield: 74percent; white solid; 1HNMR (500 MHz, CDCl3) δ 8.13–8.14 (m, 4H), 8.01 (s, 1H), 7.51–7.55(m, 6H); 13C NMR (500 MHz, CDCl3) δ 167.7, 162.1, 135.7, 131.7, 129.1, 127.5, 111.0.Under an Ar gas atmosphere, 2, 4, 6-trichloropyrimidine (18.3 g, 100 mmol), phenylboronic acid (24.4 g, 200 mmol), palladium acetate (0.56 g, 2.5 mmol), triphenylphosphine (1.31 g, 5.0 mmol), DME (930 ml) and an aqueous solution of 2M sodium carbonate (310 ml) were stirred for 15 hours at a reflux temperature. The solvent was distilled away under reduced pressure. The obtained residue was extracted by dichloromethane. The residue obtained by concentrating the organic phase was refined by silica-gel column chromatography (a developing solvent: hexane-ethyl acetate) to provide an intermediate body XAfter 2, 4, 6-nichluropyiimidin 25g(l 362mm 1), phenylbu x n c acid 36.5g(299.3mmol), and tetrakis(triphenyLphosp}tine)palladium (1.118 Q96mmoL) were dissolved in toluene (408mL), 2.OM Na, CA, aqueous solution (204 mL) and ethanol (204mL) were added thereto. The mixture was stored under influx for 2 hours at 120C. Upon completion of the reaction, extraction with EA and purification by column chromatography gave a compound 1-2 (25g, 93.7mmol, 69percent).The starting material, 2, 4, 6-trichloropyrimidine (60 g, 327 mmol) to THF (2878 mL) to dissolve after phenylboronic acid (79.8 g, 654 mmol), Pd (PPh3) 4 (22.7 g, 19.6 mmol), K2CO3 (271 g, 1962 mmol), followed by the addition of water (1440 mL), stirred and refluxed. When the reaction is complete, the ether was extracted with water, the organic layer was concentrated after then, the resulting organic was dried over MgSO4 and concentrated to silicagel column and recrystallization. To obtain the product 53.9 (Yield: 68percent)Synthesis (Synthesis of Compound 1); Under a nitrogen atmosphere, trichloropyrimidine (10 g, 54.5 mmol), phenylboronic acid (13.3 g, 109 mmol), palladium acetate (0.3 g, 1.37 mmol), triphenylphosphine (0.72 g, 2.73 mmol), dimethoxyethane (150 mL) and an aqueous solution of 2M sodium carbonate (170 mL) were added together in sequential order, and heated to reflux for 8 hours. After the reaction solution was cooled down to the room temperature, an organic layer was removed and an organic solvent was distilled away under reduced pressure. The obtained residue was refined by silica-gel column chromatography, whereby an intermediate body 1-1 (9.2g, a yield of 63percent) was obtained.Under a nitrogen atmosphere, trichloropyrimidine (10 g, 54.5 mmol), phenylboronic acid (13.3 g, 109 mmol), palladium acetate (0.3 g, 1.37 mmol), triphenylphosphine (0.72 g, 2.73 mmol), dimethoxyethane (150 mL) and an aqueous solution of 2M sodium carbonate (170 mL) were added together in sequential order, and heated to reflux for eight hours. -After the reaction solution was cooled down to the room temperature, an organic phase was removed and an organic solvent was distilled away under reduced pressure. The obtained residue was refined by silica-gel column chromatography, whereby an intermediate 5-1 (9.2 g, a yield of 63percent) was obtained.Under a nitrogen atmosphere, trichloropyrimidine (10 g, 54.5 mmol), phenylboronic acid (13.3 g, 109 mmol), palladium acetate (0.3 g, 1.37 mmol), triphenylphosphine (0.72 g, 2.73 mmol), dimethoxyethane (150 mL) and an aqueous solution of 2M sodium carbonate (170 mL) were added together in sequential order, and heated to reflux for 8 hours. After the reaction solution was cooled down to the room temperature, an organic layer was removed and an organic solvent was distilled away under reduced pressure. The obtained residue was refined by silica-gel column chromatography, whereby an intermediate body 2H-1 (9.2 g, a yield of 63percent) was obtainedPreparation of Compound G [72] 2, 4, 6-trichloropyrimidine (16.8 g, 91 mmol), phenylboronic acid (24.4 g, 200 mmol), Pd(PPh2, 4, 6-trichloropyrimidin (10g, 54.51mmol), phenylboronic acid (16.6g, 136, 29mmol), Pd(PPhPreparation of Compound 1-4 2, 4, 6-trichloropyrimidine (10 g, 54.51 mmol), phenylboronic acid (16.6 g, 136, 29 mmol), Pd(PPhExample 89; 2-Chloro-4 , 6-diphenylpyrimidine; A mixture of 2, 4, 6-trichloropyrimidine, 2.76g (15.0 mmol) , phenylboronic acid, 3.66g (30.0 mmol) , Pd(OAc)mixture of 2, 4, 6-Trichloropyrimidine, 2.76g (15.0 mmol), phenylboronic acid, 3. 66G (30. 0 mmol), Pd (OAc) 2, 86MG (0. 38 mmol), triphenylphosphine, 200mg (0.76 mmol) in 150ML of ethylene glycol dimethyl ether was heated to obtain a clear solution. To the solution was added 25mL of 4. OM aq. NA2CO3. The reaction mixture was refluxed for 24h at 70 °C. The mixture was cooled to room temperature and diluted with 100mL ethyl acetate. The organic layer was washed with water (2X50ML), sat. aq. NaCl (LX50ML), and dried (MGS04). After the solution was concentrated, the residue was recrystallized with ET2O-HEPTANE (1: 3) to afford the desired product in 1.64g (41percent) as a pale yellow SOLID. 1H NMR (CDC13): 5 8.15-8. 12 (m, 4H), 8.02 (s, 1H), 7.57-7. 51 (m, 6H).A mixture of 2, 4, 6-trichloropyrimidine, 2.76g (15.0 mmol), phenylboronic acid, 3.66g (30.0 mmol), Pd (OAc) 2, 86mg (0.38 mmol), triphenylphosphine, 200mg (0.76 mmol) in 150ML of ethylene glycol dimethyl ether was heated to obtain a clear solution. To the solution was added 25mL of 4. OM aq. NA2CO3. The reaction mixture was refluxed for 24h at 70 °C. The mixture was cooled to room temperature and diluted with LOOML ethyl acetate. The organic layer was washed with water, sat. aq. NaCl, and dried (MgS04). After the solution was concentrated, the residue was recrystallized with Et20-Heptane (1: 3) to afford the desired product in 1.64g (41percent) as a pale yellow SOLID. 1H NMR (CDC13) 8. 15-8. 12 (m, 4H), 8. 02 (s, 1H), 7.57-7. 51 (m, 6H).2-Chloro-4, 6-diphenylpyrimidine 75 g (0.41 mol) of 1, 3, 5-trichloro-pyrimidine, 100 g (0.82 mol) of phenylboronic acid and 625 ml of a 4M solution of NaHCO3 to 2.5 l of ethylene glycol dimethyl ether and the suspension was. 2.3 g (10.23 mmol) of Pd (OAc) 2 and 10.35 g (34 mmol) of P (o-Tol) 3 was added to the suspension, and the reaction mixture was refluxed underIt was heated for 16 hours.Then, the mixture was partitioned between ethyl acetate and water, the organic phase was washed with water three times, dried over Na2SO4, and evaporated in a rotary evaporator. The remaining residue was recrystallized from heptane / toluene.The yield was 43 g (0.15 mol, 38percent).Under nitrogen flow , the of 10 g of 2, 4, 6-trichloropyrimidine, 13.3g of Phenylboronic acid, 2M of Aqueous solution of sodium carbonate 163.5ml, 1, 2-dimethoxyethane 545ml with Bis(triphenylphosphine)palladium(II)dichloride mixture solution was refluxedthe for 2h . After cooling to room temperature, extraction was carried out withtoluene. The organic layer was washed twice with water, dried with sulfuricacid and evaporated. The resulting concentrate was purified by columnchromatography on silica gel and dried in vacuo to obtain 6.46 g of 2-chloro-4, 6-diphenylpyrimidine.Phenylboronic acid pinacol ester (22.3 g, 109 mmol), THF (240 ml), 2, 4, 6-trichloropyrimidine (10 g, 54.5 mmol), Pd (PPh 86.9 g (0.35 mol) of 2-hydroxy-4, 6-diphenyl-1, 3-pyrimidine (compound 2) are stirred in 400 ml (4.38 mol) of phosphoryl chloride under reflux for 6 hours. The reaction mixture is cooled to 20-25° C. and added dropwise to 4 l of water. The beige precipitate is filtered off, washed with water and dried in a vacuum oven. 89.0 g (=95.4percent yield) of beige crystals are obtained of the formula [C00058] [00401] with a melting point of 112-114° C. [00402] Examples A4 to A10 and A12 to A13 illustrate the preparation of the compounds according to the inventiona)

Molecular Weight:266.72
XLogP3:4.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:266.0610761
Monoisotopic Mass:266.0610761
Topological Polar Surface Area:25.8
Heavy Atom Count:19
Complexity:246
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes