2,2-Dimethylethenylboronicacidpinacolester

To a stirred solution/mixture of 4-amino-5-bromo-2-fluorobenzonitrile (1 g, 4.65 mol, 1 equiv), As shown in Figure 25, a benzoyl substrate 1j (0.1 mmol) was sequentially added to a 25 mL Schlenk tube.Copper pivalate (0.03 mmol), silver oxide (0.2 mmol), potassium pivalate (0.2 mmol), Cesium bicarbonate (0.2mmol), nitrogen gas was exchanged for 5 minutes for 3 times, Under a nitrogen atmosphere, 2 g (0.3 mmol) of alkenyl borate substrate, DMSO (2.0 mL) were added in sequence.Tighten the bottle cap and stir in a 45 oil bath for 12 hours.After the reaction was completed, it was cooled to room temperature, and a small amount of ethyl acetate and ammonia were added in order to quench the reaction. The ethyl acetate was repeatedly extracted.The organic layers were combined and washed with saturated brine, dried over anhydrous sodium sulfate, filtered with suction, and the solvent was distilled off under reduced pressure.The crude product was separated and purified on a preparative plate (PE: EA = 20: 1) to give 4 g (31.5 mg) of a white solid in a yield of 90%.General procedure: Condition A: To a solution of boronic acid pinacol ester derivative (2.0 equiv.), bromo derivative(1.0 equiv.), Pd[PPh3]4 (0.2 equiv.), and K2CO3 (3.6 equiv.) in 1, 4-dioxane was added a drop of waterand the reaction mixture was heated at 80 C for 15 h. After this time, a saturated aqueous NH4Clsolution was added and the aqueous phase was extracted with EtOAc three times. The combinedorganic phases were washed with brine, dried over MgSO4, filtered, and the solvent removed underreduced pressure. The residue was purified by flash column chromatography (silica gel) to obtainthe corresponding product. Condition B: Boronic acid pinacol ester derivative (1.1 equiv.), bromoderivative (1.0 equiv.), Pd[PPh3]4 (0.05 equiv.), and K2CO3 (2.0 M aqueous solution, 6.6 equiv.) weredissolved in THF and the reaction mixture was heated at 80 C for 48 h. After this time, a saturatedaqueous NH4Cl solution was added and the aqueous phase was extracted with EtOAc three times.The combined organic phases were washed with brine, dried over MgSO4, filtered, and the solventremoved under reduced pressure. The residue was purified by flash column chromatography (silica gel)to obtain the corresponding product. Conditions C: Boronic acid pinacol ester derivative (1.1 equiv.), bromo derivative (1.0 equiv.), Pd[PPh3]4 (0.05 equiv.), and K2CO3 (2.0 M aqueous solution, 6.6 equiv.)were dissolved in THF and the reaction mixture was heated at 80 C for 15 h. After this time, a saturatedaqueous NH4Cl solution was added and the aqueous phase was extracted with EtOAc three times.The combined organic phases were washed with brine, dried over MgSO4, filtered, and the solventremoved under reduced pressure. The residue was purified by flash column chromatography (silicagel) to obtain the corresponding product.General procedure: Condition A: To a solution of boronic acid pinacol ester derivative (2.0 equiv.), bromo derivative(1.0 equiv.), Pd[PPh3]4 (0.2 equiv.), and K2CO3 (3.6 equiv.) in 1, 4-dioxane was added a drop of waterand the reaction mixture was heated at 80 C for 15 h. After this time, a saturated aqueous NH4Clsolution was added and the aqueous phase was extracted with EtOAc three times. The combinedorganic phases were washed with brine, dried over MgSO4, filtered, and the solvent removed underreduced pressure. The residue was purified by flash column chromatography (silica gel) to obtainthe corresponding product. Condition B: Boronic acid pinacol ester derivative (1.1 equiv.), bromoderivative (1.0 equiv.), Pd[PPh3]4 (0.05 equiv.), and K2CO3 (2.0 M aqueous solution, 6.6 equiv.) weredissolved in THF and the reaction mixture was heated at 80 C for 48 h. After this time, a saturatedaqueous NH4Cl solution was added and the aqueous phase was extracted with EtOAc three times.The combined organic phases were washed with brine, dried over MgSO4, filtered, and the solventremoved under reduced pressure. The residue was purified by flash column chromatography (silica gel)to obtain the corresponding product. Conditions C: Boronic acid pinacol ester derivative (1.1 equiv.), bromo derivative (1.0 equiv.), Pd[PPh3]4 (0.05 equiv.), and K2CO3 (2.0 M aqueous solution, 6.6 equiv.)were dissolved in THF and the reaction mixture was heated at 80 C for 15 h. After this time, a saturatedaqueous NH4Cl solution was added and the aqueous phase was extracted with EtOAc three times.The combined organic phases were washed with brine, dried over MgSO4, filtered, and the solventremoved under reduced pressure. The residue was purified by flash column chromatography (silicagel) to obtain the corresponding product.To a solution of To a solution of 3 -bromo-5-chloro- aniline (500 mg, 2.42 mmol) in l, 4-dioxane (10 ml) and H20 (1 ml) was added 4, 4, 5, 5- tetramethyl-2-(2-methylprop- l-enyl)- 1 , 3, 2-dioxaborolane (529 mg, 2.90 mmol), Pd(dppf)Cl2 (177 mg, 0.24 mmol) and Cs2C03 (2.37 g, 7.26 mmol). The RM was heated to 120 C for 12 h under N2. The solution was concentrated in vacuo. The residue was purified by FCC (25 % EtOAc in petroleum ether) to give the title compound as a green oil (Y = 41 %). 'H NMR (400 MHz, DMSO-rf6) d ppm 6.42 (t, J= 2 Hz, 1H), 6.37 (s, 1H), 6.34 (s, 1H), 6.08 (s, 1H), 5.35 (s, 2H), 1.83 (s, 3H), 1.80 (s, 3H).To a solution of 32 2-amino-4-bromo-benzoic acid (500 mg, 2.31 mmol, 1.0 eq) in 15 1, 4-dioxane/27 water (4:1, 20 mL) under a N2 atmosphere was added 669 Compound WXOO4 (150.00 mg, 318.92 tmol) and4, 4, 5, 5-tetramethyl-2(2-methylpropan- 1 -alkenyl)-1 , 3, 2-di- oxaborolane (69.68 mg, 382.70 tmol) were dissolved in dioxane (20.00 mE) at room temperature, followed by the addition of potassium carbonate (132.23 mg, 956.75 jtmol) and water (2.00 mE). The reaction mixture was stirred at room temperature for 30 minutes under nitrogen atmosphere, followed by the addition of [1, 1 ?-bis(diphenylphosphino)ferrocene] palladium dichioride (70.01 mg, 95.68 jtmol). The reaction mixture was heated to 80 C. and stirred for 16 hours. After the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. Water (30 mE) was added to the obtained residue and extracted with ethyl acetate (20 mEx3). The organic phases were combined and dried over anhydrous sodium sulfate, followed by filtration. The filtrate was concentrated under reduced pressure. The obtained residue was isolated by preparative HPEC to obtain the target product WXOO7. MS-ESI mlz: 446.2 [M+H]. 'H NMR (400 MHz, CDC13) oe: 8.70 (s, 1H), 7.85 (s, 1H), 7.39 (s, 1H), 7.24 (d, J=7.6 Hz, 1H), 7.16 (s, 1H), 6.76 (d, J=8.0 Hz, 1H), 6.31 (s, 1H), 6.11 (s, 1H), 4.86 (dd, J=14.2, 10.2 Hz, 1H), 4.05 (dd, J=7.0, 3.4 Hz, 2H), 0.3.81 (d, J=3.2 Hz, 1H), 3.77 (s, 3H), 2.81 (s, 3H), 1.86 (s, 3H), 1.78 (s, 3H), 1.37 (t, J=6.8 Hz, 3H).Under nitrogen atmosphere, 2-methyl-1-propenylboronic acid pinacol ester (49.7 mg, 0.273 mmol) was dissolved in DME (1.6 mL). To the solution were added the compound 2 (50 mg, 0.182 mmol), PdCl2 (dppf)(13.3 mg, 0.018 mmol), potassium phosphate (116 mg, 0.546 mmol) and water (0.4 mL). The mixture was stirred under microwave irradiation at 120 C. for 30 minutes. 2-methyl-1-propenylboronic acid pinacol ester (49.7 mg, 0.273 mmol) and PdCl2 (dppf) (13.3 mg, 0.018 mmol) were added and the mixture was stirred under microwave irradiation at 130 C. for 1 hour. The reaction mixture was poured into water. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give compound 34 (30 mg, yield 56%). 1H-NMR (CDCl3) delta: 1.49 (s, 9H), 1.97 (s, 3H), 2.10 (s, 3H), 2.85 (br, 2H), 3.74 (br, 2H), 4.60 (s, 2H), 6.47 (s, 1H).

Molecular Weight:182.07
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:182.1478100
Monoisotopic Mass:182.1478100
Topological Polar Surface Area:18.5
Heavy Atom Count:13
Complexity:211
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes