1-methyl-7-oxabicyclo[4.1.0]heptane

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

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2)

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2)

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2 :EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2 :EtOAc=10:2)

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

Procedure: To a solution of 1-methyl-7-oxabicyclo[4.1.0]heptane, 30a, (1.0 g, 7.1 mmol) in water was added ammonium hydroxide (6.0 mL, 154.1 mmol). The mixture was heated to 50° C. for 48 hours. The mixture was diluted with water, extracted with EtOAc and then twice with 20% MeOH/CHCl3. The organic phases were dried (MgSO4), filtered and concentrated in vacuo to provide the desired product, 30b, as an amorphous white solid. extracted with EtOAc The organic phases were dried (MgSO4) filtered concentrated in vacuo

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2)

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

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

Procedure: To a solution of 1-methyl-7-oxabicyclo[4.1.0]heptane, 30a, (1.0 g, 7.1 mmol) in water was added ammonium hydroxide (6.0 mL, 154.1 mmol). The mixture was heated to 50° C. for 48 hours. The mixture was diluted with water, extracted with EtOAc and then twice with 20% MeOH/CHCl3. The organic phases were dried (MgSO4), filtered and concentrated in vacuo to provide the desired product, 30b, as an amorphous white solid. extracted with EtOAc The organic phases were dried (MgSO4) filtered concentrated in vacuo

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2 :EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2 :EtOAc=10:2)

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

Procedure: To a solution of 1-methyl-7-oxabicyclo[4.1.0]heptane, 30a, (1.0 g, 7.1 mmol) in water was added ammonium hydroxide (6.0 mL, 154.1 mmol). The mixture was heated to 50° C. for 48 hours. The mixture was diluted with water, extracted with EtOAc and then twice with 20% MeOH/CHCl3. The organic phases were dried (MgSO4), filtered and concentrated in vacuo to provide the desired product, 30b, as an amorphous white solid. extracted with EtOAc The organic phases were dried (MgSO4) filtered concentrated in vacuo

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

Procedure: A mixture of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.25 g), 1-methyl-1,2-epoxycyclohexane (1.31 g), benzyltrimethylammonium chloride (178 mg), 1N aqueous sodium hydroxide (7.8 ml), water (17 ml), and toluene was heated to reflux for 8 hours and 20 minutes. After the reaction mixture was cooled to room temperature, the precipitates were collected by filtration, washed with water, and dried. The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2) to give colorless crystals of 3-[2-{(1R*,2R*)-2-hydroxy-2-methylcyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine (189 mg). was heated to reflux for 8 hours and 20 minutes the precipitates were collected by filtration washed with water dried The crude material was purified by column chromatography on silica gel (CH2Cl2:EtOAc=10:2)

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