[3-(bromomethyl)phenyl]boronic acid

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (0.166 g, 1.2 mmol) was added to a solution of 2-cyclopentyl-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (0.235 g, 1 mmol) and 3-(bromomethyl)phenylboronic acid (0.257 g, 1.2 mmol) in acetone (10 mL). After stirring for 1 h at 60° C., the reaction mixture was cooled to room temperature and filtered and the filtrate was evaporated under reduced pressure to give crude 34(2-cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)phenylboronic acid as a colorless solid (0.315 g, 85%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 2H), 7.83 (s, 1H), 7.73-7.68 (m, 2H), 7.56 (s, 1H), 7.47 (d, 1H, J=7.8 Hz), 7.32 (t, 1H, J=7.8 Hz), 7.04 (d, 1H, J=8.7 Hz), 5.25 (s, 2H), 4.85-4.81 (m, 1H), 2.01-1.98 (m, 2H), 1.75-1.59 (m, 6H). LC-MS (ESI) Calcd for C19H20BNO4S [M+H]+: 370.12. Found: 369.90. the reaction mixture was cooled to room temperature filtered the filtrate was evaporated under reduced pressure

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

Procedure: To a solution of 2-cyclopentyl-5-hydroxyisoindolin-1-one (500 mg, 2.3 mmol) in acetone (20 mL), K2CO3 (1.2 g, 8.7 mmol) and 3-(bromomethyl)phenylboronic acid (650 mg, 3.0 mmol) were added and refluxed for 3 h. The reaction mixture was filtered and solvent was evaporated in vacuo to obtain 3-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)phenylboronic acid as a white solid (582.7 mg, 72%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 7.86 (s, 1H), 7.75-7.69 (m, 2H), 7.55-7.32 (m, 4H), 7.19 (s, 1H), 7.09-7.07 (m, 1H), 5.15 (s, 2H), 4.55-4.49 (m, 1H), 4.37 (s, 2H), 1.84-1.56 (m, 8H). LRMS calcd. for C20H22BNO4 [M+H]+ 352 found: 352. refluxed for 3 h The reaction mixture was filtered solvent was evaporated in vacuo

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

Procedure: A suspension of [3-(bromomethyl)phenyl]boronic acid (1.0 g, 4.6 mmol), N-methyl-methanesulfonamide (0.56 g, 5.1 mmol) and potassium carbonate (1.9 g, 14 mmol) in acetone (10 mL) was stirred for 6 hours at room temperature. The mixture was diluted with dichloromethane (50 mL), filtered through a plug of diatomaceous earth and evaporated under reduced pressure. Crude (3-{[methyl(methylsulfonyl)amino]methyl}phenyl)boronic acid was isolated as a yellow viscous oil (1.08 g, 88%). MS=266 (M+Na)+. filtered through a plug of diatomaceous earth evaporated under reduced pressure

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

Procedure: A suspension of [3-(bromomethyl)phenyl]boronic acid (1.0 g, 4.6 mmol), N-methyl-methanesulfonamide (0.56 g, 5.1 mmol) and potassium carbonate (1.9 g, 14 mmol) in acetone (10 mL) was stirred for 6 hours at room temperature. The mixture was diluted with dichloromethane (50 mL), filtered through a plug of diatomaceous earth and evaporated under reduced pressure. Crude (3-{[methyl(methylsulfonyl)amino]methyl}phenyl)boronic acid was isolated as a yellow viscous oil (1.08 g, 88%). MS=266 (M+Na)+. filtered through a plug of diatomaceous earth evaporated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (0.166 g, 1.2 mmol) was added to a solution of 2-cyclopentyl-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (0.235 g, 1 mmol) and 3-(bromomethyl)phenylboronic acid (0.257 g, 1.2 mmol) in acetone (10 mL). After stirring for 1 h at 60° C., the reaction mixture was cooled to room temperature and filtered and the filtrate was evaporated under reduced pressure to give crude 34(2-cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)phenylboronic acid as a colorless solid (0.315 g, 85%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 2H), 7.83 (s, 1H), 7.73-7.68 (m, 2H), 7.56 (s, 1H), 7.47 (d, 1H, J=7.8 Hz), 7.32 (t, 1H, J=7.8 Hz), 7.04 (d, 1H, J=8.7 Hz), 5.25 (s, 2H), 4.85-4.81 (m, 1H), 2.01-1.98 (m, 2H), 1.75-1.59 (m, 6H). LC-MS (ESI) Calcd for C19H20BNO4S [M+H]+: 370.12. Found: 369.90. the reaction mixture was cooled to room temperature filtered the filtrate was evaporated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (0.166 g, 1.2 mmol) was added to a solution of 2-cyclopentyl-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (0.235 g, 1 mmol) and 3-(bromomethyl)phenylboronic acid (0.257 g, 1.2 mmol) in acetone (10 mL). After stirring for 1 h at 60° C., the reaction mixture was cooled to room temperature and filtered and the filtrate was evaporated under reduced pressure to give crude 34(2-cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)phenylboronic acid as a colorless solid (0.315 g, 85%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 2H), 7.83 (s, 1H), 7.73-7.68 (m, 2H), 7.56 (s, 1H), 7.47 (d, 1H, J=7.8 Hz), 7.32 (t, 1H, J=7.8 Hz), 7.04 (d, 1H, J=8.7 Hz), 5.25 (s, 2H), 4.85-4.81 (m, 1H), 2.01-1.98 (m, 2H), 1.75-1.59 (m, 6H). LC-MS (ESI) Calcd for C19H20BNO4S [M+H]+: 370.12. Found: 369.90. the reaction mixture was cooled to room temperature filtered the filtrate was evaporated under reduced pressure

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

Procedure: To a solution of 2-cyclopentyl-5-hydroxyisoindolin-1-one (500 mg, 2.3 mmol) in acetone (20 mL), K2CO3 (1.2 g, 8.7 mmol) and 3-(bromomethyl)phenylboronic acid (650 mg, 3.0 mmol) were added and refluxed for 3 h. The reaction mixture was filtered and solvent was evaporated in vacuo to obtain 3-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)phenylboronic acid as a white solid (582.7 mg, 72%). The crude product was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 7.86 (s, 1H), 7.75-7.69 (m, 2H), 7.55-7.32 (m, 4H), 7.19 (s, 1H), 7.09-7.07 (m, 1H), 5.15 (s, 2H), 4.55-4.49 (m, 1H), 4.37 (s, 2H), 1.84-1.56 (m, 8H). LRMS calcd. for C20H22BNO4 [M+H]+ 352 found: 352. refluxed for 3 h The reaction mixture was filtered solvent was evaporated in vacuo

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

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

Procedure: The phenol (7.5) (400 mg, 1.02 mmol) and 3-(bromomethyl)phenylboronic acid (219 mg, 1.02 mmol) were dissolved in DMF (10 mL). Cesium carbonate (664 mg, 2.04 mmol) was added to the mixture, and the slurry was stirred for 48 hours. The reaction was then diluted with water and extracted with EtOAc (2×100 mL). The organic layers were combined and washed with a 1 M lithium chloride solution (1×50 mL) and brine (1×50 mL), and dried over magnesium sulfate. The filtrate was concentrated, and the residue was purified by medium pressure chromatography (silica gel, 30 to 100% EtOAc:hexanes) to give 34.1 (95.0 mg). MS ESI (pos.) m/e: 527.2 (M+H). extracted with EtOAc (2×100 mL) washed with a 1 M lithium chloride solution (1×50 mL) and brine (1×50 mL) dried over magnesium sulfate The filtrate was concentrated the residue was purified by medium pressure chromatography (silica gel, 30 to 100% EtOAc:hexanes)

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

Procedure: The phenol (7.5) (400 mg, 1.02 mmol) and 3-(bromomethyl)phenylboronic acid (219 mg, 1.02 mmol) were dissolved in DMF (10 mL). Cesium carbonate (664 mg, 2.04 mmol) was added to the mixture, and the slurry was stirred for 48 hours. The reaction was then diluted with water and extracted with EtOAc (2×100 mL). The organic layers were combined and washed with a 1 M lithium chloride solution (1×50 mL) and brine (1×50 mL), and dried over magnesium sulfate. The filtrate was concentrated, and the residue was purified by medium pressure chromatography (silica gel, 30 to 100% EtOAc:hexanes) to give 34.1 (95.0 mg). MS ESI (pos.) m/e: 527.2 (M+H). extracted with EtOAc (2×100 mL) washed with a 1 M lithium chloride solution (1×50 mL) and brine (1×50 mL) dried over magnesium sulfate The filtrate was concentrated the residue was purified by medium pressure chromatography (silica gel, 30 to 100% EtOAc:hexanes)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a sealed tube, 30 mg (0.14 mmol) of 3-bromomethylphenylboronic acid is dissolved in 100 μL of a 40% aqueous solution of dimethylamine and the solution is heated at 100° C. for 4 hours. The solvents are evaporated and the residue is taken up in 1.5 mL of anhydrous dioxan. The solution is degassed before adding 38 mg (0.14 mmol) of 8-bromo-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate, 13 mg (0.028 mmol) of dichlorobis(triphenylphosphine)-palladium (11) and 200 μL (0.4 mmol) of a 2M aqueous solution of tribasic potassium triphosphate. The reaction mixture is stirred at II 0° C. for 20 hours. Water is added and the product is extracted with ethyl acetate. The organic phases are washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and evaporated. The residue is purified by chromatography on silica (eluent chloroform/methanol/ammonia 90/25/4) to give 5 mg (10%) of 8-(3-dimethylaminomethyl-phenyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in the form of a beige solid. The solvents are evaporated The solution is degassed the product is extracted with ethyl acetate The organic phases are washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate filtered evaporated The residue is purified by chromatography on silica (eluent chloroform/methanol/ammonia 90/25/4)