2-CHLORO-4-PHENYLPYRIMIDINE

To a solution of 2, 4-dichloropyrimidine (149 mg, 1 mmol) in THF (5 mL), tetrakis(triphenylphosphine) palladium (23 mg, 2 mol percent) and 0.5M solution of phenylzinc bromide (2.1 mL, 1.05 mmol) in THF were added. The reaction mixture was stirred at 50° C. for overnight. Then it was added saturated ammonium chloride solution and extracted with EtOAc twice. The organic layers were combined, washed with water and dried (MgSO4). Evaporation of solvent gave a yellow residue which was purified by Prep. HPLC to afford a yellowish oil as 2-chloro-4-phenyl-pyrimidine.General procedure: Azaheteroaryl halide (1 mmol), catalyst (0.005-0.05 mol percent) and 1M aq. Na2CO3 (1.1 mL) were stirred in a mixture of H2O-EtOH(1:2, 5 mL). The arylboronic acid (1.1 mmol) was added to the above mixture and stirring was continued for required time at 60 °C. After the requisite time, reaction mixture was diluted with ethyl acetate and the catalyst was separated by centrifugation. The centrifugate was dried over anhydrous sodium sulphate and evaporated. Then the product was analyzed by GC-MS or LC-MS.The solution was concentrated and chromatographed on a silicagel column with n-hexane-ethyl acetate (4:1) as the eluting solvent to give the coupled product. The product was confirmed by 1H and 13C NMR spectral analysis. The used catalyst was washed with water, ethanol and dichloromethane, and dried under vacuum before reuse.comprising the compound B-12 (10g, 67.1mmol) was added to a round bottom flask the compound Β-11 (9. 8g, 80. 5mmol) and Pd (PPh3)4 (2. 33g, 2.01mmol) , and the round-bottom flask filled with argon. To this was added toluene (240mL), ethanol (120mL) and 2Μ K2C03 (120mL), and the mixture was stirred at reflux for 4 hours. Cooled at room temperature, after extraction with EA and washed with water, drying the resulting organic layer to give compound B-13 (11g, 86percent) was purified by column chromatography on silica.A round bottom flask containing 10 g (67.1 mmol) of the compound B-12 was charged with 9.8 g (80.5 mmol) of the compound B-11 and 2.33 g (2.01 mmol) of Pd(PPh3)4 was charged and filled with argon gas. 240 mL of toluene, 120 mL of ethanol and 120 mL of 2M K2CO3 were added and the mixture was refluxed and stirred for 4 hours. Cooled to room temperature, extracted with EA and washed with water. The obtained organic layer was dried and purified by silica column to obtain 11 g (86percent) of Compound B-13.Preparation of Compound 2-6 [130] After 2, 4-dichloropyrimidine (15 g, 100 mmol), phenyl boronic acid (12.28 g, 100 mL), Tetrakis(triphenylphosphine)palladium (5.82 g, 5 mmol), sodium carbonate (25.61 g, 240 mmol) and ethanol (200 mL) were dissolved in toluen (500 mL), the mixture was stirred under reflux for 3 hours at 70 . After extracting with EA/HA mixture of 2, 4-dichloroprymidine 5 (1.00g, 6.7mmol), phenylboronic acid (0.99g, 8.1mmol), (1, 1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.51g, 0.7mmol) and sodium carbonate (2.13g, 20.1mmol) in DMF/1, 4-dioxane/water (4:2:1, 10mL) was degassed with nitrogen and stirred at 80°C for 10h. After completion of the reaction, the reaction mixture was diluted with dichloromethane (50ml), washed with brine (30mL×3), dried over anhydrous NaTo a mixture of 2, 4-dichloropyrimidine (90) (50 mg, 0.336 mmol), phenylboronic acid (41 mg, 0.336 mmol), sodium carbonate (110 mg in 0.5 niL water) and DME (2.5 niL) was added palladium acetate (3.8 mg, 0.0168 mmol) and triphenylphosphine (8.8 mg, 0.0336 mmol). The reaction mixture was heated at 95j00469j To a stirred solution of 2, 4-dichloropyrimidine (0.200 g, 1.34 mmol, 1 equiv) in mixture of toluene and DMF (1.8/0.2 ml) was added K2C03 (0.557 g, 4.03 mmol, 1 equiv), and phenylboronic acid (0.196 g, 1.61 mmol, 1.2 equiv). The reaction mixture was irradiated in the microwave (185 °C, 10 mm), diluted with EtOAc, washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The crude brown oil was purified by chromatography on Si02 (EtOAc/hex, 1:10 to 3:7) to give a 0.140 g (55percent yield) of the desired product as a white solid.2-Chloro-4-phenylpyrimidine 2, 4-Dichloropyrimidine (5 g, 33.57 mmol) was dissolved in acetonitrile (60 ml) prior to the addition of water (15 ml). To this was added phenylboronic acid (4.09 g, 33.57 mmol) and sodium carbonate (14.23 g, 134.28 mmol). The reaction mixture was degassed for 10 min by bubbling nitrogen through it before addition of Pd(PPhTo a mixture of 2, 4-dichloropyrimidine (1.47g, 9.8mmol), benzene boronic acid (Ig, 8.2mmol), Na2CO3 (2.61g, 24.6mmol) in a mixture of DME (15ml), EtOH (2ml) and water (3ml) was added Pd(PPh3)4 (190mg, 0.16mmol) and the resulting mixture heated in a microwave at 125°C for 30 min. The reaction was repeated on same scale. The reaction mixtures were combined and diluted with water and extracted with EtOAc (x 2). The EtOAc layers were combined and washed with sat. NaCl, dried over MgSO4General procedure: A mixture of 2, 4-dichloropyrimidine (6.71 mmol), ary-boronic acid (6.71 mmol). DMF or dioxane (10 ml) was added to the above mixture followed by aqueous sodium carbonate (2 M, 6 ml, ). The reaction mixture was degassed with argon for 15 min. Pd(PPhA solution of 2, 4-dichloropyrimidine (1.OOg, 6.71 mmol), phenylboronic acid (0.90g, 7.38 mmol) in 1, 4-dioxane:water (8:2; 15 ml) was stirred at rt. The reaction mixture was degassed for 15 mm before addition of Cs2CO3 (6.56 g, 20.13 mmol) and Pd(PPh3)4 (0.39g, 0.335 mmol). The reaction mixture was heated at 110°C for 14 h. The resulting reaction mixture was cooled to rt and poured into saturated NaHCO3 solution (40 ml). The obtained mixture was extracted with EtOAc (2 x 25 ml). The combined organic phase was washed with brine solution (20 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (8percent EtOAc in hexane) yielding 2-chloro-4-phenylpyrimidine (0.45g, 2.37 mmol). LCMS: Method C, 2.23 mi MS: ES+ 191.57; ‘H NMR (400 MHz, CDC13) ppm 8.67 (d, J=5.2 Hz, 1 H), 8.11 - 8.13 (m, 2 H), 7.68 (d, J=5.6 Hz, 1 H), 7.54 - 7.58 (m, 3 H).

Molecular Weight:190.63
XLogP3:2.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:190.0297759
Monoisotopic Mass:190.0297759
Topological Polar Surface Area:25.8
Heavy Atom Count:13
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes