1-bromo-2-phenoxybenzene

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

Procedure: 1-Bromo-2-phenoxybenzene (432 mg, 1.73 mmol), piperazine (299 mg, 3.47 mmol), Pd2(dba)3 (48 mg, 0.052 mmol), BINAP (54 mg, 0.087 mmol) and NaOt-Bu (249 mg, 2.60 mmol) were dissolved in toluene (10 mL) in a reaction vessel and refluxed at 100° C. for 20 hours. After the reaction was completed, the reaction mixture was diluted with EtOAc and filtered through Celite. The filtrate was concentrated under reduced pressure and the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1) to obtain 283 mg of the target compound (1.11 mmol, 64.3%). filtered through Celite The filtrate was concentrated under reduced pressure the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1)

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

Procedure: 2-Bromophenol (1.22 mL, 11.6 mmol), phenylboronic acid (2.8 g, 23.1 mmol), Cu(OAc)2 (4.2 g, 23.1 mmol) and pyridine (4.66 mL, 57.8 mmol) were dissolved in dichloromethane (100 mL) in a reaction vessel holding 1 g of 4 Å M.S. and stirred at room temperature for 18 hours. After the reaction was completed, the reaction mixture was diluted with dichloromethane and filtered through Celite. The filtrate was extracted with 1 N NaOH and brine, and the organic layer was dried with anhydrous MgSO4 and filtered again. The filtrate was concentrated under reduced pressure) to obtain 436 mg of the target compound (1.75 mmol, 15.1%). filtered through Celite The filtrate was extracted with 1 N NaOH and brine the organic layer was dried with anhydrous MgSO4 filtered again The filtrate was concentrated under reduced pressure)

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

Procedure: To a solution of 2-bromophenol (1 g, 5.84 mmol), phenylboronic acid (1.42 g, 11.69 mmol) and TEA (2.95 g, 29.2 mmol) in DCM (30 mL) was added Cu(OAc)2 (1.05 g, 5.84 mmol) and 4 Å molecular sieves (500 mg). The reaction mixture was stirred at room temperature over air with a dry tube attached for 16 h. The mixture was filtered and the filtrate was washed by water (50 mL) and brine (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated with the residue purified by column chromatography to give 612 mg of the desired product. The mixture was filtered the filtrate was washed by water (50 mL) and brine (30 mL) The organic layer was dried over anhydrous Na2SO4 filtered concentrated with the residue purified by column chromatography

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

Procedure: To a solution of 2-bromophenol (1 g, 5.84 mmol), phenylboronic acid (1.42 g, 11.69 mmol) and TEA (2.95 g, 29.2 mmol) in DCM (30 mL) was added Cu(OAc)2 (1.05 g, 5.84 mmol) and 4 Å molecular sieves (500 mg). The reaction mixture was stirred at room temperature over air with a dry tube attached for 16 h. The mixture was filtered and the filtrate was washed by water (50 mL) and brine (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated with the residue purified by column chromatography to give 612 mg of the desired product. The mixture was filtered the filtrate was washed by water (50 mL) and brine (30 mL) The organic layer was dried over anhydrous Na2SO4 filtered concentrated with the residue purified by column chromatography

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

Procedure: A mixture of 4-chloro-7-cyclopentyl-5-iodopyrrolo[2,3-d]pyrimidine (1.26 g) and potassium (2-phenoxyphenyl)trifluoroborate (1.0 g, prepared by reacting 2-phenoxybromobenzene with butyllithium in tetrahydrofuran at -70° C. followed by triisopropyl borate (IV) followed by potassium hydrogen fluoride by a method analogous to that described in J. Org. Chem. 1995, 60, 3020-3027), in degassed toluene (40 ml), ethanol (10 ml) and water (10 ml) was stirred under nitrogen and bis(triphenylphosphine)palladium (II) chloride (0.25 g) was added followed by sodium bicarbonate (2.0 g). The mixture was stirred and heated at 105° C. for 16 hours and then cooled to ambient temperature. The mixture was separated and the upper layer was evaporated under reduced pressure to give a residue which was purified by flash column chromatography on silica using petroleum ether/ether (2:1) as a mobile phase to give 4-chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine which was used directly in the next part of this example. prepared at -70° C. cooled to ambient temperature The mixture was separated the upper layer was evaporated under reduced pressure to give a residue which was purified by flash column chromatography on silica

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

Procedure: A mixture of 4-chloro-7-cyclopentyl-5-iodopyrrolo[2,3-d]pyrimidine (1.26 g) and potassium (2-phenoxyphenyl)trifluoroborate (1.0 g, prepared by reacting 2-phenoxybromobenzene with butyllithium in tetrahydrofuran at -70° C. followed by triisopropyl borate (IV) followed by potassium hydrogen fluoride by a method analogous to that described in J. Org. Chem. 1995, 60, 3020-3027), in degassed toluene (40 ml), ethanol (10 ml) and water (10 ml) was stirred under nitrogen and bis(triphenylphosphine)palladium (II) chloride (0.25 g) was added followed by sodium bicarbonate (2.0 g). The mixture was stirred and heated at 105° C. for 16 hours and then cooled to ambient temperature. The mixture was separated and the upper layer was evaporated under reduced pressure to give a residue which was purified by flash column chromatography on silica using petroleum ether/ether (2:1) as a mobile phase to give 4-chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine which was used directly in the next part of this example. prepared at -70° C. cooled to ambient temperature The mixture was separated the upper layer was evaporated under reduced pressure to give a residue which was purified by flash column chromatography on silica

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

Procedure: 1-Bromo-2-phenoxybenzene (432 mg, 1.73 mmol), piperazine (299 mg, 3.47 mmol), Pd2(dba)3 (48 mg, 0.052 mmol), BINAP (54 mg, 0.087 mmol) and NaOt-Bu (249 mg, 2.60 mmol) were dissolved in toluene (10 mL) in a reaction vessel and refluxed at 100° C. for 20 hours. After the reaction was completed, the reaction mixture was diluted with EtOAc and filtered through Celite. The filtrate was concentrated under reduced pressure and the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1) to obtain 283 mg of the target compound (1.11 mmol, 64.3%). filtered through Celite The filtrate was concentrated under reduced pressure the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1)

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

Procedure: 1-Bromo-2-phenoxybenzene (432 mg, 1.73 mmol), piperazine (299 mg, 3.47 mmol), Pd2(dba)3 (48 mg, 0.052 mmol), BINAP (54 mg, 0.087 mmol) and NaOt-Bu (249 mg, 2.60 mmol) were dissolved in toluene (10 mL) in a reaction vessel and refluxed at 100° C. for 20 hours. After the reaction was completed, the reaction mixture was diluted with EtOAc and filtered through Celite. The filtrate was concentrated under reduced pressure and the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1) to obtain 283 mg of the target compound (1.11 mmol, 64.3%). filtered through Celite The filtrate was concentrated under reduced pressure the concentrate was purified by column chromatography (MC:mixture solution (MC:MeOH:H2O:NH3=80:20:1:1)=6:1)

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

Procedure: 2-Bromophenol (1.22 mL, 11.6 mmol), phenylboronic acid (2.8 g, 23.1 mmol), Cu(OAc)2 (4.2 g, 23.1 mmol) and pyridine (4.66 mL, 57.8 mmol) were dissolved in dichloromethane (100 mL) in a reaction vessel holding 1 g of 4 Å M.S. and stirred at room temperature for 18 hours. After the reaction was completed, the reaction mixture was diluted with dichloromethane and filtered through Celite. The filtrate was extracted with 1 N NaOH and brine, and the organic layer was dried with anhydrous MgSO4 and filtered again. The filtrate was concentrated under reduced pressure) to obtain 436 mg of the target compound (1.75 mmol, 15.1%). filtered through Celite The filtrate was extracted with 1 N NaOH and brine the organic layer was dried with anhydrous MgSO4 filtered again The filtrate was concentrated under reduced pressure)

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

Procedure: 2-Bromophenol (1.22 mL, 11.6 mmol), phenylboronic acid (2.8 g, 23.1 mmol), Cu(OAc)2 (4.2 g, 23.1 mmol) and pyridine (4.66 mL, 57.8 mmol) were dissolved in dichloromethane (100 mL) in a reaction vessel holding 1 g of 4 Å M.S. and stirred at room temperature for 18 hours. After the reaction was completed, the reaction mixture was diluted with dichloromethane and filtered through Celite. The filtrate was extracted with 1 N NaOH and brine, and the organic layer was dried with anhydrous MgSO4 and filtered again. The filtrate was concentrated under reduced pressure) to obtain 436 mg of the target compound (1.75 mmol, 15.1%). filtered through Celite The filtrate was extracted with 1 N NaOH and brine the organic layer was dried with anhydrous MgSO4 filtered again The filtrate was concentrated under reduced pressure)