3-(oxan-2-yloxy)propan-1-ol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO20111154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO20111154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-tetrahydropyranyloxy-1-propanol (1.0 g, 6.25 mmol) in DMF (10.0 mL) was added NaH (0.17 g, 95%) and stirred at 0° C. After 30 minutes, 2,5 dibromopyridine (1.0 g, 4.22 mmol) was added and the mixture was stirred at room temperature for 2 hours. The mixture was then poured into 5% cold citric acid (10.0 mL) and extracted with EtOAc (3×15 mL). The combined organic extracts were washed with water (3×15 mL), dried (Na2SO4), and concentrated to dryness. The resulting material was purified by silica gel flash chromatography using 20% EtOAc in hexane containing 0.5% triethyl amine. The appropriate fractions (monitored by TLC in 30% EtOAc in hexane) were combined and concentrated to give the desired product (1.1 g) as a colorless syrup. 1H-NMR and mass spectral data were consistent with the structure. the mixture was stirred at room temperature for 2 hours extracted with EtOAc (3×15 mL) The combined organic extracts were washed with water (3×15 mL) dried (Na2SO4) concentrated to dryness The resulting material was purified by silica gel flash chromatography concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO2011/154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO2011/154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-tetrahydropyranyloxy-1-propanol (1.0 g, 6.25 mmol) in DMF (10.0 mL) was added NaH (0.17 g, 95%) and stirred at 0° C. After 30 minutes, 2,5 dibromopyridine (1.0 g, 4.22 mmol) was added and the mixture was stirred at room temperature for 2 hours. The mixture was then poured into 5% cold citric acid (10.0 mL) and extracted with EtOAc (3×15 mL). The combined organic extracts were washed with water (3×15 mL), dried (Na2SO4), and concentrated to dryness. The resulting material was purified by silica gel flash chromatography using 20% EtOAc in hexane containing 0.5% triethyl amine. The appropriate fractions (monitored by TLC in 30% EtOAc in hexane) were combined and concentrated to give the desired product (1.1 g) as a colorless syrup. 1H-NMR and mass spectral data were consistent with the structure. the mixture was stirred at room temperature for 2 hours extracted with EtOAc (3×15 mL) The combined organic extracts were washed with water (3×15 mL) dried (Na2SO4) concentrated to dryness The resulting material was purified by silica gel flash chromatography concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO20111154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-tetrahydropyranyloxy-1-propanol (1.0 g, 6.25 mmol) in DMF (10.0 mL) was added NaH (0.17 g, 95%) and stirred at 0° C. After 30 minutes, 2,5 dibromopyridine (1.0 g, 4.22 mmol) was added and the mixture was stirred at room temperature for 2 hours. The mixture was then poured into 5% cold citric acid (10.0 mL) and extracted with EtOAc (3×15 mL). The combined organic extracts were washed with water (3×15 mL), dried (Na2SO4), and concentrated to dryness. The resulting material was purified by silica gel flash chromatography using 20% EtOAc in hexane containing 0.5% triethyl amine. The appropriate fractions (monitored by TLC in 30% EtOAc in hexane) were combined and concentrated to give the desired product (1.1 g) as a colorless syrup. 1H-NMR and mass spectral data were consistent with the structure. the mixture was stirred at room temperature for 2 hours extracted with EtOAc (3×15 mL) The combined organic extracts were washed with water (3×15 mL) dried (Na2SO4) concentrated to dryness The resulting material was purified by silica gel flash chromatography concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenol (WO2011/154734A1, which is incorporated herein by reference in it is entirety; 500 mg, 1.88 mmol), and Ph3P (986 mg, 3.76 mmol) in dry THF (10 mL) was added 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol (Can. J. Chem. Vol. 73, 1195, pp 1682, which is incorporated herein by reference in it is entirety; 452 mg, 2.82 mmol). The resulting mixture was cooled to 0° C. using an ice bath and diethylazodicarboxylate (0.69 mL, 3.76 mmol) was added to the chilled mixture which was allowed to warm up to RT. The volatiles were removed under reduced pressure. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (739 mg, 96%). LCMS (Method 1): Rt 3.63 min, m/z 408 [MH+]. to warm up to RT The volatiles were removed under reduced pressure The residue was purified by FCC