1-(2-chloroethyl)-4,4-difluoropiperidine

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

Procedure: The title compound has been prepared according to the similar manner described in 85-B (ii) using 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (100 mg, 0.218 mmol) obtained in Example 31-B-(i), potassium carbonate (75.3 mg, 0.545 mmol) and 1-(2-chloroethyl)-4,4-difluoropiperidine (80.0 mg, 0.436 mmol) obtained above. The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50) to give pure title compound (120 mg, 91%) as a colorless solid. obtained above The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50)

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

Procedure: To a solution of 4,4-difluoropiperidine (1.00 g, 6.35 mmol) in acetone (15 mL), were added potassium carbonate (2.19 g, 15.9 mmol) and 1-bromo-2-chloroethane (635 μL, 7.62 mmol) and the mixture was stirred for 8 h at 50° C. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70) to obtain title compound (188 mg, 16%) as a pale yellow oil. Insoluble materials were removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70)

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

Procedure: The title compound has been prepared according to the similar manner described in 85-B (ii) using 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (100 mg, 0.218 mmol) obtained in Example 31-B-(i), potassium carbonate (75.3 mg, 0.545 mmol) and 1-(2-chloroethyl)-4,4-difluoropiperidine (80.0 mg, 0.436 mmol) obtained above. The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50) to give pure title compound (120 mg, 91%) as a colorless solid. obtained above The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50)

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

Procedure: To a solution of 4,4-difluoropiperidine (1.00 g, 6.35 mmol) in acetone (15 mL), were added potassium carbonate (2.19 g, 15.9 mmol) and 1-bromo-2-chloroethane (635 μL, 7.62 mmol) and the mixture was stirred for 8 h at 50° C. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70) to obtain title compound (188 mg, 16%) as a pale yellow oil. Insoluble materials were removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70)

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

Procedure: The title compound has been prepared according to the similar manner described in 85-B (ii) using 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (100 mg, 0.218 mmol) obtained in Example 31-B-(i), potassium carbonate (75.3 mg, 0.545 mmol) and 1-(2-chloroethyl)-4,4-difluoropiperidine (80.0 mg, 0.436 mmol) obtained above. The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50) to give pure title compound (120 mg, 91%) as a colorless solid. obtained above The crude product was purified by basic silica gel column chromatography (EtOAc/hexane=20/80→50/50)

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

Procedure: To a solution of 4,4-difluoropiperidine (1.00 g, 6.35 mmol) in acetone (15 mL), were added potassium carbonate (2.19 g, 15.9 mmol) and 1-bromo-2-chloroethane (635 μL, 7.62 mmol) and the mixture was stirred for 8 h at 50° C. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70) to obtain title compound (188 mg, 16%) as a pale yellow oil. Insoluble materials were removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (EtOAc/hexane=0/100→30/70)