1-chloro-3-methoxypropan-2-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of pyrazole-4-boronic acid pinacol ester (0.25 g, 1.29 mmol) in THF (5 mL) was added a solution of sodium bis(trimethylsilyl)amide (0.71 mL, 2M in THF, 1.42 mmol), followed by 1-chloro-3-methoxy-2-propanol (0.24 g, 2.58 mmol). The reaction mixture was stirred in a sealed vial at 90° C. for 6 days. Additional 1-chloro-3-methoxy-2-propanol (0.24 g, 2.58 mmol) was added, followed by triethylamine (0.35 mL, 2.60 mmol). The reaction mixture was stirred at 90° C. for 3 days, then cooled to r.t. Water (2 mL) and EtOAc (5 mL) were added. The organic fraction was separated, washed with H2O (2×2 mL), then brine (2 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (0.38 g, 96%) as an orange oil that was used without further purification. LCMS (ES+) 283.0 (M+H)+, RT 2.52 minutes (Method 1). The reaction mixture was stirred at 90° C. for 3 days cooled to r.t The organic fraction was separated washed with H2O (2×2 mL) brine (2 mL), dried (MgSO4) filtered concentrated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of pyrazole-4-boronic acid pinacol ester (0.25 g, 1.29 mmol) in THF (5 mL) was added a solution of sodium bis(trimethylsilyl)amide (0.71 mL, 2M in THF, 1.42 mmol), followed by 1-chloro-3-methoxy-2-propanol (0.24 g, 2.58 mmol). The reaction mixture was stirred in a sealed vial at 90° C. for 6 days. Additional 1-chloro-3-methoxy-2-propanol (0.24 g, 2.58 mmol) was added, followed by triethylamine (0.35 mL, 2.60 mmol). The reaction mixture was stirred at 90° C. for 3 days, then cooled to r.t. Water (2 mL) and EtOAc (5 mL) were added. The organic fraction was separated, washed with H2O (2×2 mL), then brine (2 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (0.38 g, 96%) as an orange oil that was used without further purification. LCMS (ES+) 283.0 (M+H)+, RT 2.52 minutes (Method 1). The reaction mixture was stirred at 90° C. for 3 days cooled to r.t The organic fraction was separated washed with H2O (2×2 mL) brine (2 mL), dried (MgSO4) filtered concentrated in vacuo

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, from Example 519, (0.300 g, 0.000786 mol) and cesium carbonate (0.384 g, 0.00118 mol) in N,N-dimethylformamide (7.9 mL) was added 1-chloro-3-methoxy-2-propanol (0.0844 mL, 0.786 mmol) dropwise. The reaction was heated to 50° C. overnight. Sodium iodide (0.236 g, 0.00157 mol) was added and stirring was continued at 50° C. The mixture was diluted with water and methylene chloride and extracted 3 times with methylene chloride. Purify by flash chromatography then reverse-phase HPLC to obtain 520 as a white solid (22.5 mg). MS(ESI+) 470.2 was continued at 50° C extracted 3 times with methylene chloride Purify by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, from Example 519, (0.300 g, 0.000786 mol) and cesium carbonate (0.384 g, 0.00118 mol) in N,N-dimethylformamide (7.9 mL) was added 1-chloro-3-methoxy-2-propanol (0.0844 mL, 0.786 mmol) dropwise. The reaction was heated to 50° C. overnight. Sodium iodide (0.236 g, 0.00157 mol) was added and stirring was continued at 50° C. The mixture was diluted with water and methylene chloride and extracted 3 times with methylene chloride. Purify by flash chromatography then reverse-phase HPLC to obtain 520 as a white solid (22.5 mg). MS (ESI+) 470.2 was continued at 50° C extracted 3 times with methylene chloride Purify by flash chromatography

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, from Example 519, (0.300 g, 0.000786 mol) and cesium carbonate (0.384 g, 0.00118 mol) in N,N-dimethylformamide (7.9 mL) was added 1-chloro-3-methoxy-2-propanol (0.0844 mL, 0.786 mmol) dropwise. The reaction was heated to 50° C. overnight. Sodium iodide (0.236 g, 0.00157 mol) was added and stirring was continued at 50° C. The mixture was diluted with water and methylene chloride and extracted 3 times with methylene chloride. Purify by flash chromatography then reverse-phase HPLC to obtain 520 as a white solid (22.5 mg). MS (ESI+) 470.2 was continued at 50° C extracted 3 times with methylene chloride Purify by flash chromatography

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-azetidin-3-yl-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene, from Example 519, (0.300 g, 0.000786 mol) and cesium carbonate (0.384 g, 0.00118 mol) in N,N-dimethylformamide (7.9 mL) was added 1-chloro-3-methoxy-2-propanol (0.0844 mL, 0.786 mmol) dropwise. The reaction was heated to 50° C. overnight. Sodium iodide (0.236 g, 0.00157 mol) was added and stirring was continued at 50° C. The mixture was diluted with water and methylene chloride and extracted 3 times with methylene chloride. Purify by flash chromatography then reverse-phase HPLC to obtain 520 as a white solid (22.5 mg). MS(ESI+) 470.2 was continued at 50° C extracted 3 times with methylene chloride Purify by flash chromatography