[4-(morpholin-4-ylmethyl)phenyl]boronic acid;hydrochloride

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealed 5 ml microwave vial, a suspension of 2,6-dichloro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 9) (158 mg, 0.47 mmol), [4-(morpholinomethyl)phenyl]boronic acid hydrochloride (240 mg, 0.93 mmol), potassium phosphate (198 mg, 0.93 mmol) and tetrakis(triphenylphosphine)palladium (0) (16 mg, 0.01 mmol) in DMF/Water 3/1 (4 ml) was heated at 130° C. under microwave irradiation for 30 minutes. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (50 ml) and washed with NaHCO3 saturated aqueous solution (25 ml). The organic layer was separated and dried over MgSO4 before concentration to dryness under reduced pressured. The reaction crude was purified by flash column chromatography using a 12 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 2 min hold 100% A followed by a 18 min ramp to 10% B and then 5 min hold at 10% B. The desired fractions were pooled together and concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg). The product was further purified by mass directed autopreparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired material as a white solid (68 mg, 0.14 mmol, Yield 30%). The reaction was filtered through Celite™ and solvents were removed under reduced pressure washed with NaHCO3 saturated aqueous solution (25 ml) The organic layer was separated dried over MgSO4 before concentration to dryness under reduced pressured The reaction crude was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 2 min 5 min concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg) The product was further purified by mass The fractions containing product freeze dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealed microwave tube, a suspension of 2-chloro-6-fluoro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 4) (2.00 g, 6 mmol), [4-(morpholinomethyl)phenyl]boronic acid, hydrochloride, available from UORSY, (3.20 g, 12 mmol), potassium phosphate (2.63 g, 12 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.21 g, 0.19 mmol) in DMF/Water 3/1 (40 ml) was heated at 130° C. under microwave irradiation for 30 min. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (150 ml) and washed twice with NaHCO3 saturated aqueous solution (2×100 ml). The organic layer was separated, dried over MgSO4 and concentrate to dryness under reduced pressure. The reaction crude was purified by flash column chromatography using an 80 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 1 min hold 100% A, followed by a 30 min ramp to 10% B, and then 15 min hold at 10% B. The fractions containing product were pooled together and concentrated to dryness under vacuum to obtain the desired product as an off-white solid (1 g). The product was dissolved in methanol (100 ml) and 3-mercaptopropyl ethyl sulfide Silica (Phosphonics, SPM-32, 60-200 uM) was added. The suspension was stirred at room temperature over for 2 days and then at 50° C. for 1 h. After cooling to room temperature, the scavenger was filtered off and washed with methanol (30 ml). The solvent was removed under reduced pressure and the product was further purified by preparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired product as a white solid (0.6 g, 1.3 mmol, Yield 20%). The reaction was filtered through Celite™ and solvents were removed under reduced pressure washed twice with NaHCO3 saturated aqueous solution (2×100 ml) The organic layer was separated dried over MgSO4 concentrate to dryness under reduced pressure The reaction crude was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 1 min 15 min The fractions containing product concentrated to dryness under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealed microwave tube, a suspension of 2-chloro-6-fluoro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 4) (2.00 g, 6 mmol), [4-(morpholinomethyl)phenyl]boronic acid, hydrochloride, available from UORSY, (3.20 g, 12 mmol), potassium phosphate (2.63 g, 12 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.21 g, 0.19 mmol) in DMF/Water 3/1 (40 ml) was heated at 130° C. under microwave irradiation for 30 min. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (150 ml) and washed twice with NaHCO3 saturated aqueous solution (2×100 ml). The organic layer was separated, dried over MgSO4 and concentrate to dryness under reduced pressure. The reaction crude was purified by flash column chromatography using an 80 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 1 min hold 100% A, followed by a 30 min ramp to 10% B, and then 15 min hold at 10% B. The fractions containing product were pooled together and concentrated to dryness under vacuum to obtain the desired product as an off-white solid (1 g). The product was dissolved in methanol (100 ml) and 3-mercaptopropyl ethyl sulfide Silica (Phosphonics, SPM-32, 60-200 uM) was added. The suspension was stirred at room temperature over for 2 days and then at 50° C. for 1 h. After cooling to room temperature, the scavenger was filtered off and washed with methanol (30 ml). The solvent was removed under reduced pressure and the product was further purified by preparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired product as a white solid (0.6 g, 1.3 mmol, Yield 20%). The reaction was filtered through Celite™ and solvents were removed under reduced pressure washed twice with NaHCO3 saturated aqueous solution (2×100 ml) The organic layer was separated dried over MgSO4 concentrate to dryness under reduced pressure The reaction crude was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 1 min 15 min The fractions containing product concentrated to dryness under vacuum

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealed 5 ml microwave vial, a suspension of 2,6-dichloro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 9) (158 mg, 0.47 mmol), [4-(morpholinomethyl)phenyl]boronic acid hydrochloride (240 mg, 0.93 mmol), potassium phosphate (198 mg, 0.93 mmol) and tetrakis(triphenylphosphine)palladium (0) (16 mg, 0.01 mmol) in DMF/Water 3/1 (4 ml) was heated at 130° C. under microwave irradiation for 30 minutes. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (50 ml) and washed with NaHCO3 saturated aqueous solution (25 ml). The organic layer was separated and dried over MgSO4 before concentration to dryness under reduced pressured. The reaction crude was purified by flash column chromatography using a 12 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 2 min hold 100% A followed by a 18 min ramp to 10% B and then 5 min hold at 10% B. The desired fractions were pooled together and concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg). The product was further purified by mass directed autopreparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired material as a white solid (68 mg, 0.14 mmol, Yield 30%). The reaction was filtered through Celite™ and solvents were removed under reduced pressure washed with NaHCO3 saturated aqueous solution (25 ml) The organic layer was separated dried over MgSO4 before concentration to dryness under reduced pressured The reaction crude was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 2 min 5 min concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg) The product was further purified by mass The fractions containing product freeze dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealed microwave tube, a suspension of 2-chloro-6-fluoro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 4) (2.00 g, 6 mmol), [4-(morpholinomethyl)phenyl]boronic acid, hydrochloride, available from UORSY, (3.20 g, 12 mmol), potassium phosphate (2.63 g, 12 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.21 g, 0.19 mmol) in DMF/Water 3/1 (40 ml) was heated at 130° C. under microwave irradiation for 30 min. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (150 ml) and washed twice with NaHCO3 saturated aqueous solution (2×100 ml). The organic layer was separated, dried over MgSO4 and concentrate to dryness under reduced pressure. The reaction crude was purified by flash column chromatography using an 80 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 1 min hold 100% A, followed by a 30 min ramp to 10% B, and then 15 min hold at 10% B. The fractions containing product were pooled together and concentrated to dryness under vacuum to obtain the desired product as an off-white solid (1 g). The product was dissolved in methanol (100 ml) and 3-mercaptopropyl ethyl sulfide Silica (Phosphonics, SPM-32, 60-200 uM) was added. The suspension was stirred at room temperature over for 2 days and then at 50° C. for 1 h. After cooling to room temperature, the scavenger was filtered off and washed with methanol (30 ml). The solvent was removed under reduced pressure and the product was further purified by preparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired product as a white solid (0.6 g, 1.3 mmol, Yield 20%). The reaction was filtered through Celite™ and solvents were removed under reduced pressure washed twice with NaHCO3 saturated aqueous solution (2×100 ml) The organic layer was separated dried over MgSO4 concentrate to dryness under reduced pressure The reaction crude was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 1 min 15 min The fractions containing product concentrated to dryness under vacuum