3,5-Dibromobenzonitrile

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: p-Methoxybenzyl alcohol (2.6 mL) was dissolved in anhydrous DMF (50 mL) and NaH (808 mg, 60% dispersion in oil) was added in several portions. After gas evolution ceased, 3,5-dibromobenzonitrile (5.0 g) was added and the reaction mixture was stirred at 70° C. After 2 h additional amount of NaH (147 mg) was added and heating was continued for 6 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate, concentrated and purified on a silica gel column using ethyl acetate and hexanes to yield 3.1 g of the title compound (51% yield). HRMS calcd for C15H12O2BrN M+ 371.0051, observed 371.0048. heating washed with water and brine The organic extract was dried over anhydrous sodium sulfate concentrated purified on a silica gel column

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: p-Methoxybenzyl alcohol (2.6 mL) was dissolved in anhydrous DMF (50 mL) and NaH (808 mg, 60% dispersion in oil) was added in several portions. After gas evolution ceased, 3,5-dibromobenzonitrile (5.0 g) was added and the reaction mixture was stirred at 70° C. After 2 h additional amount of NaH (147 mg) was added and heating was continued for 6 h. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate, concentrated and purified on a silica gel column using ethyl acetate and hexanes to yield 3.1 g of the title compound (51% yield). HRMS calcd for C15H12O2BrN M+ 371.0051, observed 371.0048. heating washed with water and brine The organic extract was dried over anhydrous sodium sulfate concentrated purified on a silica gel column

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,5-dibromobenzonitrile (0.58 g, 2.2 mmol), phenylboronic acid (0.24 g, 2.0 mmol), Pd(PPh3)4 (0.23 g, 0.1 mmol), K2CO3 (3 mL 2 M aqueous solution) and DME (3 mL) was degassed and heated to 95° C. for 12 hr under argon. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with ethyl acetate (2×). The combined organics were dried (MgSO4) and concentrated to give the crude product which was purified with chromatography on silica gel (EtOAc/hexanes) to afford 5-bromobiphenyl-3-carbonitrile. was degassed The reaction mixture was diluted with EtOAc washed with water The aqueous layer was extracted with ethyl acetate (2×) The combined organics were dried (MgSO4) concentrated to give the crude product which was purified with chromatography on silica gel (EtOAc/hexanes)

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

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,5-dibromobenzonitrile (0.58 g, 2.2 mmol), phenylboronic acid (0.24 g, 2.0 mmol), Pd(PPh3)4 (0.23 g, 0.1 mmol), K2CO3 (3 mL 2 M aqueous solution) and DME (3 mL) was degassed and heated to 95° C. for 12 hr under argon. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with ethyl acetate (2×). The combined organics were dried (MgSO4) and concentrated to give the crude product which was purified with chromatography on silica gel (EtOAc/hexanes) to afford 5-bromobiphenyl-3-carbonitrile. was degassed The reaction mixture was diluted with EtOAc washed with water The aqueous layer was extracted with ethyl acetate (2×) The combined organics were dried (MgSO4) concentrated to give the crude product which was purified with chromatography on silica gel (EtOAc/hexanes)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of t-butylnitrite (53.5 μL, 0.449 mmoles) in 1 ml sieve dried dimethylformamide at 50° C. under an atmosphere of nitrogen was added a solution of 4-amino-3,5-dibromobenzonitrile (50 mg, 0.179 mmoles) in 1 mL of DMF. The mixture was stirred at 50° C. for 0.5 hour and partitioned between diethyl ether, ice-water, and ammonium chloride. The organic phase was separated, washed with water and brine, dried over anhydrous sodium, filtered, and evaporated. partitioned between diethyl ether, ice-water, and ammonium chloride The organic phase was separated washed with water and brine dried over anhydrous sodium filtered evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of t-butylnitrite (53.5 μL, 0.449 mmoles) in 1 ml sieve dried dimethylformamide at 50° C. under an atmosphere of nitrogen was added a solution of 4-amino-3,5-dibromobenzonitrile (50 mg, 0.179 mmoles) in 1 mL of DMF. The mixture was stirred at 50° C. for 0.5 hour and partitioned between diethyl ether, ice-water, and ammonium chloride. The organic phase was separated, washed with water and brine, dried over anhydrous sodium, filtered, and evaporated. partitioned between diethyl ether, ice-water, and ammonium chloride The organic phase was separated washed with water and brine dried over anhydrous sodium filtered evaporated

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

Procedure: 3-Bromo-5-(pyridin-3-ylamino)-benzonitrile was prepared from 3,5-dibromobenzonitrile and pyridin-3-ylamine as described for Example 36, except that the reaction was run at 130° C. This material was converted to 3-(1H-indol-4-yl)-5-(pyridin-3-ylamino)-benzonitrile by the method of Example 35. 1H NMR (400 MHz, CDCl3): δ 8.47 (s, 2H), 8.28 (d, J=4.3 Hz, 1H), 7.55-7.49 (m, 3H), 7.44 (d, J=8.2 Hz, 1H), 7.30-7.23 (m, 4H), 7.12 (dd, J=7.3, 0.9 Hz, 1H), 6.63 (t, J=2.5 Hz, 1H), 6.05 (s, 1H). was run at 130° C