tert-butyl 1-oxa-7-azaspiro[2.6]nonane-7-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol (0.065 g, 0.25 mmol), cesium carbonate (0.16 g, 0.50 mmol) and tert-butyl 1-oxa-6-azaspiro[2.6]nonane-6-carboxylate (0.068 g, 0.30 mmol) were added to 1 mL of DMF and heated to 72° C. overnight. The reaction mixture was concentrated, and DCM was added to the residue. Solids were removed by filtration and the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM to yield 74 mg of the desired product as an off-white foam. MS ESI (+) m/z 490 (M+1) detected. The reaction mixture was concentrated DCM was added to the residue Solids were removed by filtration the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM

Conditions: temp:72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol (0.065 g, 0.25 mmol), cesium carbonate (0.16 g, 0.50 mmol) and tert-butyl 1-oxa-6-azaspiro[2.6]nonane-6-carboxylate (0.068 g, 0.30 mmol) were added to 1 mL of DMF and heated to 72° C. overnight. The reaction mixture was concentrated, and DCM was added to the residue. Solids were removed by filtration and the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM to yield 74 mg of the desired product as an off-white foam. MS ESI (+) m/z 490 (M+1) detected. The reaction mixture was concentrated DCM was added to the residue Solids were removed by filtration the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM

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

Procedure: In analogy to example 82 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8=01) and 1.36 g of 80% m-chloroperbenzoic acid (MW172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M-(CH3)3COCO) method ESI+.

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

Procedure: In analogy to example 82 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8=01) and 1.36 g of 80% m-chloroperbenzoic acid (MW172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M-(CH3)3COCO) method ESI+.

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

Procedure: In analogy to example 11 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8 mmol) and 1.36 g of 80% m-chloroperbenzoic acid (MW 172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M-(CH3)3COCO) method ESI+.

Conditions: temp:72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol (0.065 g, 0.25 mmol), cesium carbonate (0.16 g, 0.50 mmol) and tert-butyl 1-oxa-6-azaspiro[2.6]nonane-6-carboxylate (0.068 g, 0.30 mmol) were added to 1 mL of DMF and heated to 72° C. overnight. The reaction mixture was concentrated, and DCM was added to the residue. Solids were removed by filtration and the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM to yield 74 mg of the desired product as an off-white foam. MS ESI (+) m/z 490 (M+1) detected. The reaction mixture was concentrated DCM was added to the residue Solids were removed by filtration the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM

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

Procedure: to a stirred solution of trimethylsulfoxonium iodide (56.1 g, 255 mmol) in anhydrous DMSO (150 ml) was added a mixture of NaH (18.5 gram 1.5 equiv., 60% in mineral oil) under a nitrogen atmosphere. The mixture was stirred at 65° C. for 1 hour, whereafter compound 2 (32 g, 150 mmol) was added as a solution in DMSO (10 ml). The mixture was refluxed overnight under a nitrogen atmosphere. The solution was allowed to reach room temperature, water was added and the mixture was extracted with diethyl ether (3×200 ml). The combined organic layer was washed with H2O, with brine and dried over Na2SO4. The Et2O was evaporated to yield 82.1 gram (32 g, 95%) compound 3. 1H-NMR (300 MHz, CDCl3): δ (ppm)=1.45 (s, 9H, BOC); 1.50-2.10 (m, 6H), 2.60-2.70 (m, 2H), 3.5-3.60 (m, 2H). The mixture was refluxed overnight under a nitrogen atmosphere to reach room temperature the mixture was extracted with diethyl ether (3×200 ml) The combined organic layer was washed with H2O, with brine dried over Na2SO4 The Et2O was evaporated

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

Procedure: In analogy to example 82 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8 mmol) and 1.36 g of 80% m-chloroperbenzoic acid (MW172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M-(CH3)3COCO) method ESI+.

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

Procedure: In analogy to example 11 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8 mmol) and 1.36 g of 80% m-chloroperbenzoic acid (MW 172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M−(CH3)3COCO) method ESI+.

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

Procedure: In analogy to example 11 step 1 with 4-methylene-azepane-1-carboxylic acid tert-butyl ester (MW: 211.307, 1.73 mmol), 1.16 g sodium bicarbonate (MW: 84.01 13.8 mmol) and 1.36 g of 80% m-chloroperbenzoic acid (MW172.57, 6.05 mmol) in 5 ml of dichloromethane. Yield: 250 mg, 63%. MS: 228.8 (M+H)+, 127.8 (M-(CH3)3COCO) method ESI+.

Conditions: temp:72.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-8-ol (0.065 g, 0.25 mmol), cesium carbonate (0.16 g, 0.50 mmol) and tert-butyl 1-oxa-6-azaspiro[2.6]nonane-6-carboxylate (0.068 g, 0.30 mmol) were added to 1 mL of DMF and heated to 72° C. overnight. The reaction mixture was concentrated, and DCM was added to the residue. Solids were removed by filtration and the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM to yield 74 mg of the desired product as an off-white foam. MS ESI (+) m/z 490 (M+1) detected. The reaction mixture was concentrated DCM was added to the residue Solids were removed by filtration the filtrate was purified on Silica gel using 6% NH4OH in MeOH and DCM