2-bromo-4-fluorobenzonitrile

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:0.00; pressure:0.00; stir:

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

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 48 mL pressure vessel containing 2-bromo-4-fluorobenzonitrile (1.00 g, 5.00 mmol), 2-oxazolidone (0.390 g, 4.50 mmol), K2CO3 (0.970 g, 7.0 mmol) and xantphos (0.231 g, 0.40 mmol) in dioxane (10 mL) was degassed with argon for 15 min. Pd2 dba3 (0.140 g, 0.15 mmol) was introduced and then the reaction mixture was heated at 70° C. for 18 h. The mixture was cooled, diluted with dioxane, and then filtered through Celite. The resulting mixture was concentrated in vacuo and subjected to column chromatography on silica gel with hexanes:ethyl acetate (1:1) to (3:7) gradient as the eluent to afford the title compound as a white solid (0.460 g, 50% yield): 1H NMR (400 MHz, CDCl3) δ ppm: 7.73 (1H, dd, J=5.8, 8.6 Hz), 7.43 (1H, dd, J=2.5, 9.6 Hz), 7.11 (1H, ddd, J=2.5, 7.5, 8.7 Hz), 4.60 (2H, t, J=7.1 Hz), 4.29 (2H, t, J=7.1 HJz); LCMS (+ESI, M+H+) m/z 207. was degassed with argon for 15 min The mixture was cooled filtered through Celite The resulting mixture was concentrated in vacuo

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 48 mL pressure vessel containing 2-bromo-4-fluorobenzonitrile (1.00 g, 5.00 mmol), 2-pyrrolidinone (0.46 mL, 6.00 mmol), Cs2CO3 (2.28 g, 7.0 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (xantphos) (0.231 g, 0.40 mmol) in dioxane (6 mL) was degassed with argon for 15 min. Pd2 dba3 was introduced and the reaction mixture heated at 105° C. for 48 h. The mixture was cooled, diluted with ethyl acetate or dioxane, and then filtered through Celite. The resulting mixture was concentrated in vacuo and subjected to column chromatography on silica gel with hexanes:ethyl acetate (3:7) gradient as the eluent to afford the title compound as a white solid (0.887 g, 87% yield): 1H NMR (400 MHz, CDCl3) δ ppm: 7.69 (1H, dd, J=5.8, 8.6 Hz), 7.22 (1H, dd, J=2.5, 9.6 Hz), 7.07 (1H, ddd, J 2.5, 7.6, 8.6 Hz), 3.96 (2H, t, J=7.0 Hz), 2.62 (2H, t, J=8.1 Hz), 2.30–2.22 (2H, m); LCMS (+ESI, M+H+) m/z 205. was degassed with argon for 15 min Pd2 dba3 was introduced The mixture was cooled diluted with ethyl acetate or dioxane filtered through Celite The resulting mixture was concentrated in vacuo

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

Procedure: 2-Bromo-4-fluorobenzonitrile was coupled to 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane as described in Example 7 part c) to give 5,2′-difluoro-5′-nitrobiphenyl-2-carbonitrile as a black solid: δH (360 MHz, CDCl3) 7.25-7.33 (2H, m), 7.40-7.44 (1H, m), 7.86 (1H, dd, J 9 and 6), 8.35-8.42 (2H, m).

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

Procedure: 2-Bromo-4-fluorobenzonitrile was coupled to 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane as described in Example 7 part c) to give 5,2′-difluoro-5′-nitrobiphenyl-2-carbonitrile as a black solid: δH (360 MHz, CDCl3) 7.25-7.33 (2H, m), 7.40-7.44 (1H, m), 7.86 (1H, dd, J 9 and 6), 8.35-8.42 (2H, m).

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

Procedure: Compound (97c) (0.140 g) was dissolved in DMF (1.7 mL), and sodium hydride (0.024 g, a 55% dispersion in paraffin liquid) was added to the resulting solution at 0° C., followed by stirring for 10 min. Then, 2-bromo-4-fluorobenzonitrile (0.112 g) was added to the reaction solution, followed by stirring at 50° C. for 30 min. Ice water was added to the reaction solution, and the precipitate was collected by filtration and was dried under reduced pressure to obtain compound (97d) (0.160 g, 69%) as a white solid. by stirring at 50° C. for 30 min the precipitate was collected by filtration was dried under reduced pressure