2-chloro-4-iodobenzonitrile

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

Procedure: Using the same reaction conditions as in Example 14, 1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (I-14b: 150 mg, 0.8465 mmol) was reacted with 2-chloro-4-iodo-benzonitrile (245.3 mg, 0.9311 mmol), 1,4-dioxane (20 mL), copper iodide (16.1 mg, 0.08465 mmol), trans-1,2-diamino cyclohexane (12.6 mg, 0.1100 mmol) and potassium phosphate (30.6 mL, 0.254 mmol) to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3). The residue was washed with hexane and dried to afford 85 mg of the product (32% yield). to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3) The residue was washed with hexane dried

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

Procedure: Using the same reaction conditions as in Example 14, 1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (I-14b: 150 mg, 0.8465 mmol) was reacted with 2-chloro-4-iodo-benzonitrile (245.3 mg, 0.9311 mmol), 1,4-dioxane (20 mL), copper iodide (16.1 mg, 0.08465 mmol), trans-1,2-diamino cyclohexane (12.6 mg, 0.1100 mmol) and potassium phosphate (30.6 mL, 0.254 mmol) to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3). The residue was washed with hexane and dried to afford 85 mg of the product (32% yield). to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3) The residue was washed with hexane dried

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (30.5 g, 0.2 mol) in 1:1 diethyl ether/3M HCl (600 mL) at 0° C. was treated dropwise over 15 minutes with a solution of sodium nitrite (18 g, 0.26 mol) in water (100 mL), stirred 15 minutes, then treated with a solution of potassium iodide (50 g, 0.3 mol) in water (50 mL) dropwise over 45 minutes, warmed to room temperature, and stirred for 1.5 hours. The organic phase was washed with water (3×100 mL) and the combined aqueous layers were extracted with diethyl ether. The combined organic layers were combined, washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes:ethyl acetate, triturated in hexanes, filtered, and dried to provide the desired product. stirred for 1.5 hours The organic phase was washed with water (3×100 mL) the combined aqueous layers were extracted with diethyl ether washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes ethyl acetate, triturated in hexanes filtered dried

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (30.5 g, 0.2 mol) in 1:1 diethyl ether/3M HCl (600 mL) at 0° C. was treated dropwise over 15 minutes with a solution of sodium nitrite (18 g, 0.26 mol) in water (100 mL), stirred 15 minutes, then treated with a solution of potassium iodide (50 g, 0.3 mol) in water (50 mL) dropwise over 45 minutes, warmed to room temperature, and stirred for 1.5 hours. The organic phase was washed with water (3×100 mL) and the combined aqueous layers were extracted with diethyl ether. The combined organic layers were combined, washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes:ethyl acetate, triturated in hexanes, filtered, and dried to provide the desired product. stirred for 1.5 hours The organic phase was washed with water (3×100 mL) the combined aqueous layers were extracted with diethyl ether washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes ethyl acetate, triturated in hexanes filtered dried

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (30.5 g, 0.2 mol) in 1:1 diethyl ether/3M HCl (600 mL) at 0° C. was treated dropwise over 15 minutes with a solution of sodium nitrite (18 g, 0.26 mol) in water (100 mL), stirred 15 minutes, then treated with a solution of potassium iodide (50 g, 0.3 mol) in water (50 mL) dropwise over 45 minutes, warmed to room temperature, and stirred for 1.5 hours. The organic phase was washed with water (3×100 mL) and the combined aqueous layers were extracted with diethyl ether. The combined organic layers were combined, washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes:ethyl acetate, triturated in hexanes, filtered, and dried to provide the desired product. stirred for 1.5 hours The organic phase was washed with water (3×100 mL) the combined aqueous layers were extracted with diethyl ether washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes ethyl acetate, triturated in hexanes filtered dried

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

Procedure: Using the same reaction conditions as in Example 14, 1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (I-14b: 150 mg, 0.8465 mmol) was reacted with 2-chloro-4-iodo-benzonitrile (245.3 mg. 0.9311 mmol), 1,4-dioxane (20 mL), copper iodide (16.1 mg, 0.08465 mmol), trans-1,2-diamino cyclohexane (12.6 mg, 0.1100 mmol) and potassium phosphate (30.6 mL, 0.254 mmol) to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3). The residue was washed with hexane and dried to afford 85 mg of the product (32% yield). to afford the crude product which was purified by column chromatography on silica gel (2% MeOH in CHCl3) The residue was washed with hexane dried

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (30.5 g, 0.2 mol) in 1:1 diethyl ether/3M HCl (600 mL) at 0° C. was treated dropwise over 15 minutes with a solution of sodium nitrite (18 g, 0.26 mol) in water (100 mL), stirred 15 minutes, then treated with a solution of potassium iodide (50 g, 0.3 mol) in water (50 mL) dropwise over 45 minutes, warmed to room temperature, and stirred for 1.5 hours. The organic phase was washed with water (3×100 mL) and the combined aqueous layers were extracted with diethyl ether. The combined organic layers were combined, washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes:ethyl acetate, triturated in hexanes, filtered, and dried to provide the desired product. stirred for 1.5 hours The organic phase was washed with water (3×100 mL) the combined aqueous layers were extracted with diethyl ether washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes ethyl acetate, triturated in hexanes filtered dried