3-CYANOPYRIDINE-5-BORONIC ACID PINACOL ESTER

In a 2 L three-necked flask, 100 g of Intermediate 3-1, 186 g of Intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added, followed by 800 ml of toluene, 200 ml of ethanol, 200 ml of water, Nitrogen gas was introduced, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 C for refluxing for 8 h. TLC was used to monitor the reaction of the starting material to room temperature and filtered to remove insoluble. The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to afford 101.6 g of Intermediate 3. The yield was 86.8%.100 g of intermediate 2-1, 186 g of intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added to a 2 L three-necked flask, and 800 ml of toluene, 200 ml of ethanol, and 200 ml of water were successively added. Nitrogen gas was added, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 C for refluxing for 8 hours. The TLC was used to monitor the reaction of the starting materials and then cooled to room temperature.The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to obtain 107.9 g of intermediate 2 in a yield of 92.2%.100 g of intermediate 2-1, 186 g of intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added to a 2 L three-necked flask, and 800 ml of toluene, 200 ml of ethanol, and 200 ml of water were successively added. Nitrogen gas was added, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 C for refluxing for 8 hours. The TLC was used to monitor the reaction of the starting materials and then cooled to room temperature.The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to obtain 107.9 g of intermediate 2 in a yield of 92.2%.100 g of intermediate 1-1, 186 g of intermediate 1-2, 203 g of potassium carbonate, 23.7 g of tetrabutylammonium bromide (TBAB) were added to a 2 L three-necked flask, and 800 ml of toluene, 200 ml of ethanol, and 200 ml of water were sequentially added. Nitrogen gas was introduced, stirred for 15 min, 2.1 g of tetrakis(triphenylphosphine)palladium was added, and the mixture was heated to 80 °C for refluxing for 8 h. TLC was used to monitor the reaction of the starting material to room temperature and filtered to remove insoluble.The impurities were separated, and the organic phase was washed with water until neutral. After drying over anhydrous sodium sulfate, the residue was purified by silica gel column to obtain 104.5 g of intermediate 1 in a yield of 89.3percent.To a 20 mL vial was added (((2, 2?-dimethyl-[1, 1?-biphenylj-3, 3?-diyl)bis(methylene))bis(oxy))bis(6-formyl-3, 1 -phenylene) bis(trifluoromethanesulfonate) (279 mg, 0.34mmol), N-(4-Bromo-3-{[(d imethylami no)methylidene]su lfamoyl}phenyl)-2-(2-ch lorophenyl)acetamide (250 mg, 545 pmol) and 5-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyridine-3- carbonitrile (125 mg, 545 pmol) were dissolved in n-propanol (10 ml) andbis(triphenylphosphine)palladium(l I) dichloride (CAS 13965-03-2) (19.2 mg, 27.2 pmol) and triphenylphosphine (7.15 mg, 27.2 pmol) were added. The solution was purged with argon for 5 minutes and aq. potassium carbonate (1.6 ml, 1.0 M, 1.6 mmol) was added. The reaction was heated at 100C for lh. Afterwards the mixture was filtered over Celite, the solvent was removed under reduced pressure and ethyl acetate and water wereadded. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over Whatmanfilter and the solvent was removed under reduced pressure.The crude was used in the next step without further purification.25 mL of the reaction flask was added hydrazine hydrate (0.25 mmol)5-Cyano-pyridine-3-boronic acid pinacol ester (0.5mmol), Cesium carbonate (1.0 mmol), Water (2.5 mmol)And polyethylene glycol-2000 (2.0 g).The reaction mixture was reacted at 120 C until the reaction was complete.The reaction mixture was cooled to room temperature, The product was isolated by column chromatography after evaporation of the solvent under reduced pressure, Yield 85%.

Molecular Weight:230.07
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:230.1226579
Monoisotopic Mass:230.1226579
Topological Polar Surface Area:55.1
Heavy Atom Count:17
Complexity:332
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes