5-Fluoro-2-iodotoluene

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

Procedure: 3.44 mL (45.8 mmol) 1-propanol are added to 3.42 g (30.5 mmol) KOtBu in 18 mL DMF at 0° C. After stirring the solution for 10 min at rt, 1.80 g (7.63 mmol) 4-fluoro-1-iodo-2-methylbenzene are added and the mixture is stirred at 80° C. for 3 h. The reaction is quenched by the addition of sat. aq. NH4Cl solution and extracted with EtOAc (2×). The combined organic layers are washed with sat. aq. NH4Cl solution and brine, dried over sodium sulphate and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1). the mixture is stirred at 80° C. for 3 h The reaction is quenched by the addition of sat. aq. NH4Cl solution extracted with EtOAc (2×) The combined organic layers are washed with sat. aq. NH4Cl solution and brine dried over sodium sulphate the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1)

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

Procedure: (4-Ethynyl-pyridin-2-yl)-urea (75 mg, 0.47 mmol), 4-fluoro-1-iodo-2-methyl-benzene (224 mg, 0.931 mmol), triethylamine (5.0 mL), palladium bis(triphenylphosphine)dichloride (16 mg, 0.023 mmol) and Copper (I) iodide (8.8 mg, 0.047 mmol) are mixed in DMF (1.8 mL). The reaction mixture is stirred for 16 hrs at room temperature before saturated NH4Cl solution (5 mL) is added along with water (25 mL). The mixture is extracted with EtOAc (3×20 mL) and the organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 5%) affords 25 mg of the desired product. The mixture is extracted with EtOAc (3×20 mL) concentrated to give the crude product Purification by silica flash column chromatography

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

Procedure: 3.44 mL (45.8 mmol) 1-propanol are added to 3.42 g (30.5 mmol) KOtBu in 18 mL DMF at 0° C. After stirring the solution for 10 min at rt, 1.80 g (7.63 mmol) 4-fluoro-1-iodo-2-methylbenzene are added and the mixture is stirred at 80° C. for 3 h. The reaction is quenched by the addition of sat. aq. NH4Cl solution and extracted with EtOAc (2×). The combined organic layers are washed with sat. aq. NH4Cl solution and brine, dried over sodium sulphate and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1). the mixture is stirred at 80° C. for 3 h The reaction is quenched by the addition of sat. aq. NH4Cl solution extracted with EtOAc (2×) The combined organic layers are washed with sat. aq. NH4Cl solution and brine dried over sodium sulphate the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1)

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

Procedure: 5-Fluoro-2-iodotoluene (3 g, 12.7 mmol) was stirred in DMF (40 mL) under argon and Zn(CN)2 (1.94 g, 16.5 mmol) and Pd(PPh3)4 (1.47 g, 1.27 mmol) were added. The reaction was stirred at 80° C. for 1.5 hours. The reaction was partitioned between ethyl acetate and water and the organic layer was washed with brine and dried over anhydrous Na2-SO4. The solvent was removed under reduced pressure to afford a yellow solid (2.90 g), confirmed by GC MS. The reaction was partitioned between ethyl acetate and water the organic layer was washed with brine dried over anhydrous Na2-SO4 The solvent was removed under reduced pressure

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

Procedure: 5-Fluoro-2-iodotoluene (3 g, 12.7 mmol) was stirred in DMF (40 mL) under argon and Zn(CN)2 (1.94 g, 16.5 mmol) and Pd(PPh3)4 (1.47 g, 1.27 mmol) were added. The reaction was stirred at 80° C. for 1.5 hours. The reaction was partitioned between ethyl acetate and water and the organic layer was washed with brine and dried over anhydrous Na2-SO4. The solvent was removed under reduced pressure to afford a yellow solid (2.90 g), confirmed by GC MS. The reaction was partitioned between ethyl acetate and water the organic layer was washed with brine dried over anhydrous Na2-SO4 The solvent was removed under reduced pressure

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper(I) iodide (102 mg) was added to a mixture of picolinic acid (66.1 mg), 4-(2-aminopyridin-3-yl)phenol (500 mg), tripotassium phosphate (1710 mg), 4-fluoro-1-iodo-2-methylbenzene (761 mg) and DMSO (8 mL). The mixture was stirred at 130° C. under nitrogen for 5 hr. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Water was added and the extracted organic layer was washed with brine. Silica-gel was added to the organic layer and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) to give the title compound (354 mg) as a yellow solid. Activated carbon was added the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) Water was added the extracted organic layer was washed with brine Silica-gel was added to the organic layer the volatiles were removed in vacuo was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)

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

Procedure: 3.44 mL (45.8 mmol) 1-propanol is added to an ice cold mixture of 3.42 g (30.5 mmol) KOtBu in 18 mL DMF. After stirring the mixture for 10 min 1.80 g (7.63 mmol) 4-fluoro-1-iodo-2-methylbenzene are added and the reaction mixture is stirred at 80° C. for 3 h. The reaction is quenched by the addition of a sat. aq. NH4Cl solution and extracted with EtOAc (2×). The combined organic layers are washed with sat. aq. NH4Cl solution and brine, dried with Na2SO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1). are added The reaction is quenched by the addition of a sat. aq. NH4Cl solution extracted with EtOAc (2×) The combined organic layers are washed with sat. aq. NH4Cl solution and brine dried with Na2SO4 the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper(I) iodide (102 mg) was added to a mixture of picolinic acid (66.1 mg), 4-(2-aminopyridin-3-yl)phenol (500 mg), tripotassium phosphate (1710 mg), 4-fluoro-1-iodo-2-methylbenzene (761 mg) and DMSO (8 mL). The mixture was stirred at 130° C. under nitrogen for 5 hr. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Water was added and the extracted organic layer was washed with brine. Silica-gel was added to the organic layer and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) to give the title compound (354 mg) as a yellow solid. Activated carbon was added the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) Water was added the extracted organic layer was washed with brine Silica-gel was added to the organic layer the volatiles were removed in vacuo was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper(I) iodide (102 mg) was added to a mixture of picolinic acid (66.1 mg), 4-(2-aminopyridin-3-yl)phenol (500 mg), tripotassium phosphate (1710 mg), 4-fluoro-1-iodo-2-methylbenzene (761 mg) and DMSO (8 ml). The mixture was stirred at 130° C. under nitrogen for 5 hr. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Water was added and the extracted organic layer was washed with brine. Silica-gel was added to the organic layer and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) to give the title compound (354 mg) as a yellow solid. Activated carbon was added the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) Water was added the extracted organic layer was washed with brine Silica-gel was added to the organic layer the volatiles were removed in vacuo was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper(I) iodide (102 mg) was added to a mixture of picolinic acid (66.1 mg), 4-(2-aminopyridin-3-yl)phenol (500 mg), tripotassium phosphate (1710 mg), 4-fluoro-1-iodo-2-methylbenzene (761 mg) and DMSO (8 mL). The mixture was stirred at 130° C. under nitrogen for 5 hr. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Water was added and the extracted organic layer was washed with brine. Silica-gel was added to the organic layer and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) to give the title compound (354 mg) as a yellow solid. Activated carbon was added the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) Water was added the extracted organic layer was washed with brine Silica-gel was added to the organic layer the volatiles were removed in vacuo was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)

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

Procedure: (4-Ethynyl-pyridin-2-yl)-urea (75 mg, 0.47 mmol), 4-fluoro-1-iodo-2-methyl-benzene (224 mg, 0.931 mmol), triethylamine (5.0 mL), palladium bis(triphenylphosphine)dichloride (16 mg, 0.023 mmol) and Copper (I) iodide (8.8 mg, 0.047 mmol) are mixed in DMF (1.8 mL). The reaction mixture is stirred for 16 hrs at room temperature before saturated NH4Cl solution (5 mL) is added along with water (25 mL). The mixture is extracted with EtOAc (3×20 mL) and the organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 5%) affords 25 mg of the desired product. The mixture is extracted with EtOAc (3×20 mL) concentrated to give the crude product Purification by silica flash column chromatography

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

Procedure: 3.44 mL (45.8 mmol) 1-propanol are added to 3.42 g (30.5 mmol) KOtBu in 18 mL DMF at 0° C. After stirring the solution for 10 min at rt, 1.80 g (7.63 mmol) 4-fluoro-1-iodo-2-methylbenzene are added and the mixture is stirred at 80° C. for 3 h. The reaction is quenched by the addition of sat. aq. NH4Cl solution and extracted with EtOAc (2×). The combined organic layers are washed with sat. aq. NH4Cl solution and brine, dried over sodium sulphate and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1). the mixture is stirred at 80° C. for 3 h The reaction is quenched by the addition of sat. aq. NH4Cl solution extracted with EtOAc (2×) The combined organic layers are washed with sat. aq. NH4Cl solution and brine dried over sodium sulphate the solvent is removed in vacuo The crude product is purified by column chromatography (silica gel, heptane/EtOAc 9/1)