3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[3.1.0]hexane-6-carboxylic acid

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (185 mg, 0.812 mmol) prepared in Example 3, hydroxybenzotriazole (132 mg, 0.975 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (187 mg, 0.975 mmol) were dissolved in 3.0 mL of methylene chloride and the (5-isobutyl-3-aminomethyl-1-phenyl)pyrazole (205 mg, 0.894 mmol) prepared in Example 9 was added dropwise. After stirring for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=1:2). After the reaction was completed, the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate. The organic layer was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (hexane:ethyl acetate=1:2) to obtain 328 mg (92.1%) of the target compound. the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate The organic layer was dried with anhydrous sodium sulfate filtered concentrated under reduced pressure separated by column chromatography (hexane:ethyl acetate=1:2)

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (252 mg, 1.11 mmol) prepared in Example 3, benzotriazole (180 mg, 1.33 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (255 mg, 1.33 mmol) were dissolved in 3.0 mL of methylene chloride and diisopropylethylamine (232 μL, 1.33 mmol) was added dropwise. After adding 2 M ammonia solution (2.49 mL, 4.98 mmol) dissolved in methanol dropwise at 0° C., the mixture was stirred at room temperature for 4 hours. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=15:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and washed with saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 177 mg (70.6%) of the target compound. washed with saturated sodium chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure separated by column chromatography (CH2Cl2:MeOH=15:1)

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

Procedure: The tert-butyl 6-ethoxycarbonyl-3-azabicyclo[3.1.0]hexane-3-carboxylate exo-isomer (613 mg, 2.40 mmol) prepared in Example 2 was dissolved in 6 mL of ethanol and 2N NaOH (2.40 mL, 4.80 mmol) was added dropwsie at 0° C. After stirring at room temperature for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=6:1). After the reaction was completed, the reaction mixture was concentrated under reduced pressure and then extracted by adding methylene chloride and water. After removing the organic layer containing byproducts, the aqueous layer was acidified with 1N HCl and extracted with methylene chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain 527 mg (96.5%) of the target compound. prepared in Example 2 the reaction mixture was concentrated under reduced pressure extracted by adding methylene chloride and water After removing the organic layer containing byproducts extracted with methylene chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (185 mg, 0.812 mmol) prepared in Example 3, hydroxybenzotriazole (132 mg, 0.975 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (187 mg, 0.975 mmol) were dissolved in 3.0 mL of methylene chloride and the (5-isobutyl-3-aminomethyl-1-phenyl)pyrazole (205 mg, 0.894 mmol) prepared in Example 9 was added dropwise. After stirring for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=1:2). After the reaction was completed, the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate. The organic layer was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (hexane:ethyl acetate=1:2) to obtain 328 mg (92.1%) of the target compound. the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate The organic layer was dried with anhydrous sodium sulfate filtered concentrated under reduced pressure separated by column chromatography (hexane:ethyl acetate=1:2)

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (252 mg, 1.11 mmol) prepared in Example 3, benzotriazole (180 mg, 1.33 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (255 mg, 1.33 mmol) were dissolved in 3.0 mL of methylene chloride and diisopropylethylamine (232 μL, 1.33 mmol) was added dropwise. After adding 2 M ammonia solution (2.49 mL, 4.98 mmol) dissolved in methanol dropwise at 0° C., the mixture was stirred at room temperature for 4 hours. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=15:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and washed with saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 177 mg (70.6%) of the target compound. washed with saturated sodium chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure separated by column chromatography (CH2Cl2:MeOH=15:1)

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

Procedure: The tert-butyl 6-ethoxycarbonyl-3-azabicyclo[3.1.0]hexane-3-carboxylate exo-isomer (613 mg, 2.40 mmol) prepared in Example 2 was dissolved in 6 mL of ethanol and 2N NaOH (2.40 mL, 4.80 mmol) was added dropwsie at 0° C. After stirring at room temperature for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=6:1). After the reaction was completed, the reaction mixture was concentrated under reduced pressure and then extracted by adding methylene chloride and water. After removing the organic layer containing byproducts, the aqueous layer was acidified with 1N HCl and extracted with methylene chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain 527 mg (96.5%) of the target compound. prepared in Example 2 the reaction mixture was concentrated under reduced pressure extracted by adding methylene chloride and water After removing the organic layer containing byproducts extracted with methylene chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: The tert-butyl 6-ethoxycarbonyl-3-azabicyclo[3.1.0]hexane-3-carboxylate exo-isomer (613 mg, 2.40 mmol) prepared in Example 2 was dissolved in 6 mL of ethanol and 2N NaOH (2.40 mL, 4.80 mmol) was added dropwsie at 0° C. After stirring at room temperature for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=6:1). After the reaction was completed, the reaction mixture was concentrated under reduced pressure and then extracted by adding methylene chloride and water. After removing the organic layer containing byproducts, the aqueous layer was acidified with 1N HCl and extracted with methylene chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain 527 mg (96.5%) of the target compound. prepared in Example 2 the reaction mixture was concentrated under reduced pressure extracted by adding methylene chloride and water After removing the organic layer containing byproducts extracted with methylene chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (185 mg, 0.812 mmol) prepared in Example 3, hydroxybenzotriazole (132 mg, 0.975 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (187 mg, 0.975 mmol) were dissolved in 3.0 mL of methylene chloride and the (5-isobutyl-3-aminomethyl-1-phenyl)pyrazole (205 mg, 0.894 mmol) prepared in Example 9 was added dropwise. After stirring for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=1:2). After the reaction was completed, the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate. The organic layer was dried with anhydrous sodium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (hexane:ethyl acetate=1:2) to obtain 328 mg (92.1%) of the target compound. the mixture was extracted with methylene chloride after adding water and saturated sodium bicarbonate The organic layer was dried with anhydrous sodium sulfate filtered concentrated under reduced pressure separated by column chromatography (hexane:ethyl acetate=1:2)

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

Procedure: The 3-(tert-butoxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid (252 mg, 1.11 mmol) prepared in Example 3, benzotriazole (180 mg, 1.33 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (255 mg, 1.33 mmol) were dissolved in 3.0 mL of methylene chloride and diisopropylethylamine (232 μL, 1.33 mmol) was added dropwise. After adding 2 M ammonia solution (2.49 mL, 4.98 mmol) dissolved in methanol dropwise at 0° C., the mixture was stirred at room temperature for 4 hours. The completion of the reaction was confirmed by TLC (CH2Cl2:MeOH=15:1). After the reaction was completed, the reaction mixture was diluted with methylene chloride and washed with saturated sodium chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and separated by column chromatography (CH2Cl2:MeOH=15:1) to obtain 177 mg (70.6%) of the target compound. washed with saturated sodium chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure separated by column chromatography (CH2Cl2:MeOH=15:1)

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

Procedure: The tert-butyl 6-ethoxycarbonyl-3-azabicyclo[3.1.0]hexane-3-carboxylate exo-isomer (613 mg, 2.40 mmol) prepared in Example 2 was dissolved in 6 mL of ethanol and 2N NaOH (2.40 mL, 4.80 mmol) was added dropwsie at 0° C. After stirring at room temperature for 3 hours, the completion of the reaction was confirmed by TLC (hexane:ethyl acetate=6:1). After the reaction was completed, the reaction mixture was concentrated under reduced pressure and then extracted by adding methylene chloride and water. After removing the organic layer containing byproducts, the aqueous layer was acidified with 1N HCl and extracted with methylene chloride. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain 527 mg (96.5%) of the target compound. prepared in Example 2 the reaction mixture was concentrated under reduced pressure extracted by adding methylene chloride and water After removing the organic layer containing byproducts extracted with methylene chloride The organic layer was dried with anhydrous magnesium sulfate filtered concentrated under reduced pressure