(2,6-dichlorophenyl)boronic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in Example 76, STEP B, but heating at 90° C. for 14 hrs, substituting 4-iodoaniline and 2,6-dichlorophenylboronic acid for 4-bromo-3-methylaniline and 4-chlorophenylboronic acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (300 mg, 0.614 mmol) (see Ex. 2, part B), 2,6-dichlorophenylboronic acid (0.921 mmol), potassium fluoride (88.6 mg, 1.84 mmol), palladium acetate (1.3 mg, 0.14 μmol), and 2-(dicyclohexylphosphino)biphenyl (4.3 mg, 12.3 μmol) were combined under N2, to which anhydrous THF (1.23 mL) was added. The yellow mixture was heated at reflux for 12 h. After cooling to room temperature, the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL). The layers were separated, and the aqueous phase was back-extracted with Et2O (10 mL). Combined organic phases were dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes) to yield the desired product as an oil. Rf=0.50 in 1:4 ethyl acetate:hexanes; MS (EI) 554.2 (M+H)+. was added The yellow mixture was heated at reflux for 12 h the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL) The layers were separated the aqueous phase was back-extracted with Et2O (10 mL) Combined organic phases were dried over Na2SO4 concentrated The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-2,6-dichlorobenzene (2.00 g) was dissolved in freshly distilled THF (7 mL). This solution was cooled to −78° C. and n-BuLi (8.3 mL of a 1.6M solution in hexane) was added dropwise to the cold solution under N2. The mixture was stirred for 5 min at −78° C. and (MeO)3B (2.2 mL) was added. The resulting mixture was allowed to warm to room temperature and stirred overnight. Water was added and the resulting mixture was stirred for 0.5 h, then acidified with HOAc and extracted with EtOAc. The organic layer was further washed with water and brine, dried (MgSO4) filtered and evaporated to yield 2,6-dichlorobenzeneboronic acid (1.6 g) to warm to room temperature stirred overnight the resulting mixture was stirred for 0.5 h extracted with EtOAc The organic layer was further washed with water and brine dried (MgSO4) filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 0.045 (0.15 mmol) 3-benzyloxy-5-bromo-1-methyl-1H-pyridin-2-one, 0.44 g (0.23 mmol) 2,6-dichlorophenylboronic acid, and 0.006 g (0.008 mmol) dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane adduct in 2 mL THF was added 1 mL 1 M aq Cs2CO3. The resulting mixture was microwaved to 160° C. for 10 min. After cooling, the organic phase was separated and concentrated and the resulting residue was re-dissolved in MeOH. 0.02 mg (0.019 mmol) 10% Pd/C was added and the resulting suspension was stirred under 1 atm hydrogen gas overnight. The reaction mixture was filtered and concentrated. Purification by automated mass-guided HPLC afforded 0.045 g (11%) 5-(2,4-dichloro-phenyl)-3-hydroxy-1-methyl-1H-pyridin-2-one. 1H NMR (499 MHz, DMSO-d6): δ 9.29 (s, 1 H); 7.71 (d, J=2.13 Hz, 1 H); 7.48 (dd, J=8.32, 2.19 Hz, 1 H); 7.43 (d, J=8.30 Hz, 1 H); 7.34 (d, J=2.35 Hz, 1 H); 6.82 (d, J=2.35 Hz, 1 H); 3.53 (s, 3 H). High resolution mass spec (FT/ICR) calc (M+H)+=270.0084 found 270.0083. The resulting mixture was microwaved to 160° C. for 10 min After cooling the organic phase was separated concentrated the resulting residue was re-dissolved in MeOH The reaction mixture was filtered concentrated Purification by automated mass-guided HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in Example 76, STEP B, but heating at 90° C. for 14 hrs, substituting 4-iodoaniline and 2,6-dichlorophenylboronic acid for 4-bromo-3-methylaniline and 4-chlorophenylboronic acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (300 mg, 0.614 mmol) (see Ex. 2, part B), 2,6-dichlorophenylboronic acid (0.921 mmol), potassium fluoride (88.6 mg, 1.84 mmol), palladium acetate (1.3 mg, 0.14 μmol), and 2-(dicyclohexylphosphino)biphenyl (4.3 mg, 12.3 μmol) were combined under N2, to which anhydrous THF (1.23 mL) was added. The yellow mixture was heated at reflux for 12 h. After cooling to room temperature, the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL). The layers were separated, and the aqueous phase was back-extracted with Et2O (10 mL). Combined organic phases were dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes) to yield the desired product as an oil. Rf=0.50 in 1:4 ethyl acetate:hexanes; MS (EI) 554.2 (M+H)+. was added The yellow mixture was heated at reflux for 12 h the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL) The layers were separated the aqueous phase was back-extracted with Et2O (10 mL) Combined organic phases were dried over Na2SO4 concentrated The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(2-Iodo-6-methyl-3-pyridyl)oxy]-6,7-dimethoxyquinoline (compound 116) (84 mg), 2,6-dichlorophenylboronic acid (191 mg), and tetrakistriphenylphosphine palladium (12 mg) were dissolved in toluene (1 ml) to prepare a solution. A saturated aqueous sodium hydrogencarbonate solution (1 ml) was added to the solution, and the mixture was stirred at 80° C. for 3 hr. The reaction solution was filtered, the solvent was then removed by distillation under the reduced pressure, and the residue was purified by column chromatography using methanol-chloroform to give the title compound (79 mg, yield 90%). to prepare a solution The reaction solution was filtered the solvent was then removed by distillation under the reduced pressure the residue was purified by column chromatography