1-phenylethenylboronic 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:0.00; pressure:0.00; stir:

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

Procedure: A solution of 1-tert-butyl-3,5-diiodo-2-methoxybenzene (4.94 g, 11.87 mmol) in dimethoxyethane (50 mL) and water (30 mL) was treated with 1-phenylvinylboronic acid (2.283 g, 15.43 mmol), tetrakis(triphenylphosphine)palladium(0) (0.686 g, 0.593 mmol) and sodium bicarbonate (2.492 g, 29.7 mmol) followed by heating at 100° C. for 3 hours. 1 N HCl was added and the mixture was extracted with ethyl acetate, then dried (Na2SO4), filtered and concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate to give the title compound. the mixture was extracted with ethyl acetate dried (Na2SO4) filtered concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate

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

Procedure: A suspension of 8-bromo-2-chloroquinazoline (Ark Pharm, Inc., Libertyville, Ill.; 2.00 g, 8.21 mmol), (1-phenylvinyl)boronic acid (Aldrich; 1.215 g, 8.21 mmol), potassium carbonate (2.384 g, 17.25 mmol), and Pd(PPh3)4 (0.190 g, 0.164 mmol) in toluene (75 mL) was stirred under argon at 90° C. for 2.5 d. The reaction was cooled to 25° C. and partitioned between EtOAc (200 mL) and water (100 mL). The organic layer was separated, sequentially washed with water (2×80 mL) and brine (80 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% hexanes/DCM) furnished 8-bromo-2-(1-phenylvinyl)quinazoline (380 mg, 1.221 mmol, 15% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 9.36 (1H, s), 8.20 (1H, s), 7.88 (1H, d, J=8.0 Hz), 7.58-7.65 (2H, m), 7.44-7.51 (2H, m), 7.40-7.44 (2H, m), 6.84 (1H, s), 5.99 (1H, s). m/z (ESI, +ve) 311.0 (M+H)+. The reaction was cooled to 25° C. partitioned between EtOAc (200 mL) and water (100 mL) The organic layer was separated sequentially washed with water (2×80 mL) and brine (80 mL) dried over Na2SO4 filtered concentrated in vacuo Chromatographic purification of the residue (silica gel, 0-100% hexanes/DCM)

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

Procedure: A mixture of 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 200 mg, 0.672 mmol), (1-phenylvinyl)boronic acid (Aldrich; 139.1 mg, 0.941 mmol), PdCl2(APhos)2 (23.8 mg, 0.034 mmol), and KOAc (131.8 mg, 1.34 mmol) in EtOH (3.4 mL) was stirred under argon in a sealed tube at 80° C. for 23 h. The mixture was concentrated onto silica gel, and chromatographically purified (silica gel, 0-10% MeOH/DCM) to provide 2-(2-(1-phenylvinyl)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (189.2 mg, 0.518 mmol, 77% yield) as an orange solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.05 (1H, br. s.), 8.23 (1H, d, J=8.8 Hz), 8.08 (1H, d, J=7.4 Hz), 7.81 (1H, d, J=8.6 Hz), 7.64 (1H, d, J=8.0 Hz), 7.54 (1H, d, J=7.8 Hz), 7.46-7.52 (2H, m), 7.41-7.46 (3H, m), 7.14 (1H, s), 6.01 (1H, s), 5.85 (1H, s), 5.47 (1H, br. s.), 3.47 (2H, td, J=6.9, 1.9 Hz), 2.33 (2H, t, J=6.8 Hz). m/z (ESI, +ve) 366.2 (M+H)+. The mixture was concentrated onto silica gel chromatographically purified (silica gel, 0-10% MeOH/DCM)

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

Procedure: A mixture of 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 200 mg, 0.672 mmol), (1-phenylvinyl)boronic acid (Aldrich; 139.1 mg, 0.941 mmol), PdCl2(APhos)2 (23.8 mg, 0.034 mmol), and KOAc (131.8 mg, 1.34 mmol) in EtOH (3.4 mL) was stirred under argon in a sealed tube at 80° C. for 23 h. The mixture was concentrated onto silica gel, and chromatographically purified (silica gel, 0-10% MeOH/DCM) to provide 2-(2-(1-phenylvinyl)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (189.2 mg, 0.518 mmol, 77% yield) as an orange solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.05 (1H, br. s.), 8.23 (1H, d, J=8.8 Hz), 8.08 (1H, d, J=7.4 Hz), 7.81 (1H, d, J=8.6 Hz), 7.64 (1H, d, J=8.0 Hz), 7.54 (1H, d, J=7.8 Hz), 7.46-7.52 (2H, m), 7.41-7.46 (3H, m), 7.14 (1H, s), 6.01 (1H, s), 5.85 (1H, s), 5.47 (1H, br. s.), 3.47 (2H, td, J=6.9, 1.9 Hz), 2.33 (2H, t, J=6.8 Hz). m/z (ESI, +ve) 366.2 (M+H)+. The mixture was concentrated onto silica gel chromatographically purified (silica gel, 0-10% MeOH/DCM)

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

Procedure: A solution of 1-tert-butyl-3,5-diiodo-2-methoxybenzene (4.94 g, 11.87 mmol) in dimethoxyethane (50 mL) and water (30 mL) was treated with 1-phenylvinylboronic acid (2.283 g, 15.43 mmol), tetrakis(triphenylphosphine)palladium(0) (0.686 g, 0.593 mmol) and sodium bicarbonate (2.492 g, 29.7 mmol) followed by heating at 100° C. for 3 hours. 1 N HCl was added and the mixture was extracted with ethyl acetate, then dried (Na2SO4), filtered and concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate to give the title compound. the mixture was extracted with ethyl acetate dried (Na2SO4) filtered concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate

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

Procedure: A solution of 1-tert-butyl-3,5-diiodo-2-methoxybenzene (4.94 g, 11.87 mmol) in dimethoxyethane (50 mL) and water (30 mL) was treated with 1-phenylvinylboronic acid (2.283 g, 15.43 mmol), tetrakis(triphenylphosphine)palladium(0) (0.686 g, 0.593 mmol) and sodium bicarbonate (2.492 g, 29.7 mmol) followed by heating at 100° C. for 3 hours. 1 N HCl was added and the mixture was extracted with ethyl acetate, then dried (Na2SO4), filtered and concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate to give the title compound. the mixture was extracted with ethyl acetate dried (Na2SO4) filtered concentrated in vacuo to give crude product which was purified by silica gel flash chromatography eluting with 50:1 hexanes/ethyl acetate

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

Procedure: A mixture of (1-phenylvinyl)boronic acid (24.0 mg, 0.000162 mol) and 4-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (50.0 mg, 0.000127 mol) in toluene (2.00 mL, 0.0188 mol) and ethanol (0.50 mL, 0.0086 mol) was treated with potassium carbonate (35 mg, 0.00025 mol) in water (1.00 mL, 0.0555 mol). The mixture was degassed by bubbling nitrogen. Tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.00001 mol) was added and nitrogen was bubbled for 3 min. The reaction was heated in a sealed tube in the microwave at 100° C. for 30 min. The reaction was allowed to cool to rt and partitioned between ethyl acetate and water. The combined organic layer was dried over MgSO4, filtered and concentrated to give the crude material The crude product was purified by FCC on silica gel eluting with EtOAc/Hexanes (1:5) to give 4-[4-(1-phenylvinyl)-1H-pyrazol-1-yl]-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]-pyridine as a solid residue, LC/MS (M+H)+: 417. The mixture was degassed by bubbling nitrogen nitrogen was bubbled for 3 min to cool to rt partitioned between ethyl acetate and water The combined organic layer was dried over MgSO4 filtered concentrated to give the crude material The crude product was purified by FCC on silica gel eluting with EtOAc/Hexanes (1:5)

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

Procedure: A mixture of (1-phenylvinyl)boronic acid (24.0 mg, 0.000162 mol) and 4-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (50.0 mg, 0.000127 mol) in toluene (2.00 mL, 0.0188 mol) and ethanol (0.50 mL, 0.0086 mol) was treated with potassium carbonate (35 mg, 0.00025 mol) in water (1.00 mL, 0.0555 mol). The mixture was degassed by bubbling nitrogen. Tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.00001 mol) was added and nitrogen was bubbled for 3 min. The reaction was heated in a sealed tube in the microwave at 100° C. for 30 min. The reaction was allowed to cool to rt and partitioned between ethyl acetate and water. The combined organic layer was dried over MgSO4, filtered and concentrated to give the crude material The crude product was purified by FCC on silica gel eluting with EtOAc/Hexanes (1:5) to give 4-[4-(1-phenylvinyl)-1H-pyrazol-1-yl]-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]-pyridine as a solid residue, LC/MS (M+H)+: 417. The mixture was degassed by bubbling nitrogen nitrogen was bubbled for 3 min to cool to rt partitioned between ethyl acetate and water The combined organic layer was dried over MgSO4 filtered concentrated to give the crude material The crude product was purified by FCC on silica gel eluting with EtOAc/Hexanes (1:5)