5,5'-Dibromo-2,2'-bipyridyl

To the 250 ml 2-neck flask was added 2, 5-Dibromopyridine (8 g, 33.8 mmol), hexamethylditin (5.53 g, 0.0169 mmol) and Pd (PPh3) 4 (0.80 g)And the mixture was heated with stirring for 72 hours.After completion of the reaction, the temperature was lowered to room temperature, After the excess ether was added, the resulting solid product was filtered and subjected to column chromatography using chloroform and methanol to obtain 4.21 g (yield: 80percent) of Compound AWith m-xylene as the solvent, 2, 5-dibromopyridine (5.0 mmol) was addedReacts with n-butyltin (5.5 mmol), Using tetrakis(triphenylphosphine)palladium as a catalyst, the reaction was carried out at 130°C in the dark for three days. After the reaction, ethylenediaminetetraacetic acid disodium salt was added to remove the remaining tin reagent. The organic phase was collected by extracting the mixture with dichloromethane and concentrating. The crude product was isolated by column chromatography to give the pure product. Yield: 80percent.A reaction vessel was charged with 6.0 g of 2, 5-dibromopyridine, 7.0 ml of bistributyltin, and 120 ml of xylene, followed by heating and stirring at 60°C for 15 minutes. Further, 700 mg of tetrakis(triphenylphosphine)palladium was added thereto, followed by stirring at 120°C for 8 hours. After cooling to room temperature, the insoluble materials were removed by filtration, and the filtrate was washed with 150 ml of an aqueous ethylenediamine tetraacetate solution. The organic layer was dehydrated with anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (carrier: silica gel, eluent: cyclohexane/toluene) to obtain 1.7 g (yield 42percent) of 5, 5'-dibromo-[2, 2']bipyridine as a yellow powder.2, 2′-bipyridine (1, 4.99 g, 0.032 mol) and bromine (10.24 g, 0.064 mol) were first added in a hydrothermal reaction container andheated to 150 °C and annealed for 15 h. Then, the mixture was cooledand the hard solidwas powdered and following treatedwith Na2SO3 solutionto remove the unreacted bromine. Finally itwas basifiedwith sodiumhydroxide and filtered. The white solid product 5, 5′-dibromo-2, 2′-bipyridine was obtained by the chromatography on silica(CH2Cl2). 5, 5′-dibromo-2, 2′-bipyrimidine, 8.64 g (86percent). m.p. 221.6–222.1 °C. 1H-NMR (400 MHz, CDCl3, δ): 7.95 (d, 2H), 8.28 (s, 2H), 8.71(d, 2H); 13C-NMR (100 MHz, CDCl3, δ): 121.47 (C5), 122.25 (C3), 139.64 (C4); 150.28 (C6), 153.64 (C2); IR (KBr): 3049 (C\H, stretching), 1562, 1453, 1356 (Ar, stretching), 636 (C\Br, stretching).Anal. calcd for C10H6N2Br2: C 38.22, H 1.91, N 8.92, Br 50.95; found: C38.26, H 1.94, N 8.90, Br 50.97.2, 2'-bipyridyl (4.99 g, 0.032 mol) and liquid bromine (10.24 g, 0.064 mol)Put into a reaction kettle at a pressure of 2.0 atm at 150 ° C for 15 hours, then cool to room temperature after the reaction, pulverize the solid, add to the Na2SO3 solution and stir to remove unreacted bromine, filter, and alkalizate the acid with a 5percent NaOH solution. , filtration, to obtain a crude product, column separation with ethyl acetate / petroleum ether, 8.64 g of white 5, 5'-dibromo-2, 2'-bipyridine was obtained in a yield of 91percent.3-Bromo-6-iodopyridine (Tokyo Chemical Industry Co., Ltd., 11.3 g), Dissolved in dehydrated toluene (Wako Pure Chemical Industries, Ltd., 320 ml), hexabutyl distannane (Bu 3 SnSnBu 3, Tokyo Chemical Industry Co., Ltd., 10 ml), tetrakistriphenylphosphine palladium (0) (Tokyo Chemical Industry Co., , The mixture was degassed by nitrogen bubbling for 1 hour, and reacted with stirring at 120 ° C. for 3 days. After the reaction, the temperature was returned to room temperature, washed with water, the organic layer was dried over sodium sulfate, filtered and concentrated, and the residue was purified by silica gel column chromatography to obtain 4.4 g of 5, 5'-dibromo-2, 2'-bipyridine Obtained3-Bromo-6-iodopyridine (Tokyo Chemical Industry Co., Ltd., 11.3 g), Hexabutyl distannane(Bu3SnSnBu3, Tokyo Chemical Industry Co., Ltd., 10 ml), Tetrakistriphenylphosphine palladium (0)(Tokyo Chemical Industry Co., Ltd., 1.2 g) was dissolved in dehydrated toluene(Wako Pure Chemical Industries, Ltd., 320 ml)Degassed by nitrogen bubbling for 1 hour, and reacted with stirring at 120 ° C. for 3 days.After the reaction, the temperature was returned to room temperature, then washed with water, the organic layer was dried with sodium sulfate, filtered and concentrated, The residue was purified by silica gel column chromatography, 4.4 g of 5, 5'-dibromo-2, 2'-bipyridine was obtained.Synthesis was confirmed by 1 H-NMR measurement (FIG. 6).5-Bromo-2-iodopyridine (6.60 g, 23.2 mmol) and Pd(PPh3)4 (0.72 g, 0.6 mmol) were dissolved in anhydrous PhMe (120 mL) under N2. Hexa-n-butylditin (7.25 g, 12.5 mmol)was added and the solution heated at reflux for 3 days. The mixture was filtered through celite and the solvent removed. The residue was chromatographed on silica using a DCM to EtOAc gradient. The resulting residue was crystallised from EtOAc/hexanes to give the 5, 5’- dibromo-2, 2’-bipyridine (1.22 g, 33 percent) as a pale yellow powder. The crystallisation liquors were evaporated under reduced pressure and the residue dissolved in DCM, hexanes wereadded and the volume of solvent reduced. The resulting precipitate was collected by filtration and air dried to give a second crop of the product (0.46 g, 13 percent) as a cream powder.5, 5'-Dibromo-2, 2'-bipyridine 2-(3-hydroxy-pentane-3-yl)-5-bromo-pyridine(Batch Process) A toluene solution (24 mL) containing 2, 5-dibromopyridine (21.11 mmoles) ad 3-pentanone (21.11 mmoles) were placed in a 125 mL jacketed flask under N2 at 20 C. in an ice bath. n-BuLi in hexanes (17.2 mL, 1.3 M, 22.36 moles; 1.06 equiv) was added via a syringe pump delivering at 0.25 mL/min. The mixture was stirred for 5 min and then quenched with 30 mL of MeOH. The reaction mixture was diluted with EtOAc (10 'L in 1 mL EtOAc) and analyzed by GC/MS. The major product was 2-(3-hydroxy-pentane-3-yl)-5-bromo-pyridine (55.33percent) indicating selective lithiation at the 2 position. The major product was isolated and purified by column chromatography to afford 33percent isolated yield.

Molecular Weight:313.98
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:313.88772
Monoisotopic Mass:311.88977
Topological Polar Surface Area:25.8
Heavy Atom Count:14
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes