6-Bromo-2,4′-bipyridine

Synthesis Example 19: Synthesis of Intermediate 16 3.08 g (13 mmol) of 2, 5-dibromo pyridine, 1.23 g (10 mmol) of 4-pyridyl boronic acid, 0.58 g (0.5 mmol) of Pd(PPhSynthesis of Intermediate 12; 6.16 g (26 mmol) of 2, 5-dibromopyridine, 2.46 g (20 mmol) of 4-pyridylboronic acid, 1.16 g (1 mmol) of Pd(PPhGeneral procedure: Boronic acid or ester (10.0 mmol), KSynthesis of Intermediate 1d; 181.16 g (764.72 mmol) of 2, 6-dibromo pyridine and 132 g (955.9 mmol) of K9- (naphthalen-1-yl) -7-phenyl-5 (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-7H-benzo [c] carbazole (1 .4g), 6- bromo-2, 4'-bipyridine (0.7 g), bis (dibenzylideneacetone) palladium (0) (0.2 g), tricyclohexylphosphine (0.2 g), tripotassium phosphate ( K3PO4) (4.1g) and 1, 2, 4-trimethylbenzene (pseudo cumene) to the flask containing (9 ml) was stirred for 2 hours at reflux temperature. The reaction mixture was cooled to room temperature, after water and added to separate liquid toluene, and the solvent was evaporated under reduced pressure. The resulting solid was washed with methanol, after further heating washing with heptane, the amino group-modified silica gel (NH DM1020: manufactured by Fuji Silysia) column chromatography was purified (eluent toluene / ethyl acetate mixed solvent). At this time, gradually increasing the ratio of ethyl acetate in developing solution to elute the desired product. The solvent was evaporated under reduced pressure, the resulting solid was heated and dissolved in toluene, subjected to re-precipitation by addition of methanol, a compound represented by the formula (1-237), 5 - ([2, 4'-bipyridine] -6-yl) was obtained 9-a (naphthalen-1-yl) -7-Fell -7H- benzo [c] carbazole (0.2 g).Pitching 100 mL flask was charged with intermediate (3) 0.5 g (0.943 mmol), 6-bromo-2, 4 '- bipyridine (6-bromo-2, 4'-bipyridine) 0.148 g (0.628 mmol) and Pd ( PPh3) 4 then the insert 46 mg (0.021 mmol) was dissolved in Toluene 6 mL EtOH and 3 mL under a nitrogen atmosphere, was added a 2M K2CO3 solution 1 mL was stirred under reflux. After the reaction was terminated, cooled to room temperature and 5 mL of H2OIt was added. Drying the mixture and then extracted twice with MC 10 mL extract with Na2SO4, filtered and concentrated under a reduced pressure. Purification of the resulting compound was purified by silica gel column chromatography to obtain a compound of orange solid (5-22, HSB-06-013) 0.07 g (yield: 20%) was obtained.Synthesis Example 17 Synthesis of Compound 27 Compound 27 was synthesized in the same manner as in Synthesis Example 1, except that naphthalen-2-yl-2-boronic acid was used instead of phenyl boronic acid (Compound A-6) in the synthesis of Intermediate 6-6 and Synthesis Example 5 Synthesis of Compound 49 Compound 49 was synthesized in the same manner as in Synthesis Example 1, except that phenanthren-9-yl-9-boronic acid was used instead of phenyl boronic acid (Compound A-6) in the synthesis of Intermediate 6-6 and General procedure: 1.92 g (5.09 mmol) of Intermediate I-4, 0.34 g (2.99 mmol)Phenyl boronic acid (compound B), 0.29 g (0.25 mmol)Tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) and 0.62 g (4.48 mmol) of K2CO3 were dissolved in 60 mL of the mixtureTetrahydrofuran (THF) and H2O (in a 2:1 volume)The solution was obtained to obtain a solution which was then stirred at 70C for about 5 hours.The reaction solution was cooled to room temperature and 40 mL of water was added thereto.It was then extracted three times with 50 mL of diethyl ether. The organic layer was collected and dried over magnesium sulfate to evaporate the solvent. The residue was separated and purified using silica gel column chromatography to obtain 0.82 g of Intermediate I-5 (yield: 74%).General procedure: Pd(OAc)2 (0.37 mmol), BINAP (0.37 mmol) and NaOtBu (10.30 mmol) were sequentially added to a stirred, degassed solution of aryl halide (3.68 mmol) and amine (7.36 mmol) in a mixture of toluene (50 mL) and DMF (5 mL) and the mixture was heated at 90 C for 4-5 h. The mixture was cooled to 20 C, diluted with Et2O (200 mL), washed with water (3 × 50 mL), washed with brine (50 mL), dried and the solvent was evaporated. The residue was purified by column chromatography, eluting with an appropriate blend of EtOAc/pet. ether, to give the Buchwald product.Synthesis of Compound 1; 6.0 g (12.63 mmol) of Intermediate 1c and 2.7 g (11.48 mmol) of Intermediate 1d were added to a mixed solvent of 4.76 g (34.4 mmol) potassium carbonate solution and THF, 398 mg (3 mol%) of Pd(PPh3)4 was added thereto while stirring, and the mixture was heated for 12 hours. The mixture was cooled to room temperature and subjected to extraction using dichloromethane. Then, an organic layer was collected, and the solvent was removed by drying the organic layer using anhydrous magnesium sulfate under reduced pressure. The resulting product was filtered using column chromatography (ethyl acetate:dichloromethane=3:7) to obtain 5.3 g of yellow solid Compound 1 (Yield: 80%). 1H NMR (500MHz, CDCl3) delta 8.73(d, 1H), 8.49(d, 1H), 8.18-8.10(m, 5H), 8.05(dd, 2H), 8.01(d, 1H), 7.97(d, 1H), 7.88(d, 1H), 7.84(m, 1H), 7.80-7.62(m, 13H), and 7.36(dd, 2H).Synthesis Synthesis of Compound 8; Compound 8 was synthesized according to Reaction Scheme 3 below: [Show Image] Intermediate 8d was synthesized by reacting Compound 1d with 4-bromophenylboronic acid through a Suzuki coupling reaction. 6.27 g (18 mmol) of Intermediate 8c and 4.67 g (15 mmol) of Intermediate 8d were added to a mixed solvent of THF and K2CO3 solution, 0.52 g (3 mol%) of Pd(PPh3)4 was added thereto while stirring, and the mixture was heated for 12 hours. The mixture was cooled to room temperature and subject to extraction using dichloromethane. Then, an organic layer was collected, and the solvent was removed by drying the organic layer using anhydrous magnesium sulfate under reduced pressure. The resulting product was filtered using column chromatography (ethyl acetate:dichloromethane=3:7) to obtain 6.8 g of yellow solid Compound 8 (Yield: 85%). 1H NMR (500MHz, CDCl3) delta 8.79(dd, 2H), 8.41(d, 2H), 8.12-8.08(m, 3H), 8.06-7.93(m, 5H), 7.87-7.79(m, 3H), 7.74(dd, 2H), 7.69-7.60(m, 5H), 7.38-7.31(m, 4H).Step A: Preparation of 6-((S)-2-Amino-3-phenylpropylamino)-2-(4-pyridyl)pyridine: A neat mixture of Synthesis Example 19: Synthesis of Intermediate 16 [Show Image] 3.08 g (13 mmol) of 2, 5-dibromo pyridine, 1.23 g (10 mmol) of 4-pyridyl boronic acid, 0.58 g (0.5 mmol) of Pd(PPh3)4, and 5.53 g (40 mmol) of K2CO3 were dissolved in 50 ml of a mixed solution of THF/H2O (2:1), and the mixture was stirred at 80C for 5 hours. The mixture was subjected to extraction three times with 60 mL of diethyl ether. An organic layer was collected and dried using magnesium sulfate to evaporate the solvent. The residue was recrystallized with dichloromethane and normal hexane to obtain 1.74 g (yield: 74%) of Intermediate 16. This compound was identified using HR-MS. C10H7BrN2 Calculated value: 233.9793; Measured value: 233.9796Synthesis of Intermediate 12; 6.16 g (26 mmol) of 2, 5-dibromopyridine, 2.46 g (20 mmol) of 4-pyridylboronic acid, 1.16 g (1 mmol) of Pd(PPh3)4, and 11.1 g (80 mmol) of K2CO3 were dissolved in 100 mL of a THF/H2O (2:1) mixed solution and stirred at a temperature of 80C for 5 hours. The reaction solution was extracted three times with 100 ml of diethylether. An organic layer was collected and dried using magnesium sulfate to evaporate the solvent. The residue was re-crystallized with dichloromethane and normal hexane to obtain 3.47 g (Yield: 72%) of Intermediate 12. The generated compound was identified using HR-MS. C10H7BrN2 calc.: 233.9793; found 233.9795General procedure: Boronic acid or ester (10.0 mmol), K2CO3 (25.0 mmol) in H2O (10 mL) and Pd(PPh3)4 (0.3 mmol) were added sequentially to a solution of aryl halide (10.0 mmol) in 1, 4-dioxane (40 mL). The reaction mixture was stirred at 90 C for 2-20 h and was then cooled to 20 C and partitioned between EtOAc (200 mL) and H2O (100 mL). The organic phase was washed with water (3 × 50 mL), washed with brine (50 mL), dried and the solvent was evaporated. The residue was purified by column chromatography, eluting with an appropriate gradient of EtOAc/pet. ether, to give the Suzuki product.Synthesis of Intermediate 1d; 181.16 g (764.72 mmol) of 2, 6-dibromo pyridine and 132 g (955.9 mmol) of K2CO3 were dissolved in a mixed solution of 1, 4-dioxane and H2O (v/v=1000 mL:500 mL). 47 g (382.36 mmol) of pyridine-4-boronic acid, 7 g (7.65 mmol) of tris(dibenzylideneacetone)di-palladium and P(o-Tolyl)3 were added thereto and the mixture was refluxed for 12 hours while heating at 105C. After the reaction was completed, the mixture was cooled to room temperature and washed with ethyl acetate while being filtered with Cellite. The resulting product was subjected to extraction twice using ethyl acetate by adding a NaCl solution to a water layer. The resulting product was dried using MgSO4, concentrated, filtered using column chromatography (Hex:EA=1:1), and suspension-stirred in a Hexane(30mL)-Ether(10mL) solution, and then filtered to obtain 22.5 g of Intermediate 1d (Yield: 25%). 1H NMR (300MHz, CDCl3) delta 7.52(d, 1H), 7.66(t, 1H), 7.76(d, 1H) 7.87(d, 2H), 8.73(d, 2H).Step B:

Molecular Weight:235.08
XLogP3:2.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:233.97926
Monoisotopic Mass:233.97926
Topological Polar Surface Area:25.8
Heavy Atom Count:13
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes