3-Azabicyclo[3.1.0]hexane-3-carboxylicacid,6-amino-,1,1-dimethylethylester,

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (7.3 g, 25.3 mmol) and triethylorthoformate (24 mL, 152 mmol) in acetic acid (200 mL) was added sodium azide (9.9 g, 152 mmol) and the resulting mixture was set under inert atmosphere. The mixture was heated at 100° C. for 4 h and then cooled to RT at which time the volatiles were removed in vacuo. The residue was taken up in ethyl acetate (200 mL) and washed with aqueous sodium bicarbonate solution, followed by brine. The organics were dried over sodium sulfate, filtered, and concentrate to dryness under vacuum. The residue was placed in the refrigerator overnight and the next day a solid white precipitate was observed. The precipitate was triturated with hexane and the solvent was carefully decanted to give the title compound 3.2 g (50.3%) as a white solid. ESI-MS calculated for C11H17N5O2: Exact Mass: 251.28. Found 252.28. cooled to RT at which time the volatiles were removed in vacuo washed with aqueous sodium bicarbonate solution The organics were dried over sodium sulfate filtered concentrate to dryness under vacuum was placed in the refrigerator overnight The precipitate was triturated with hexane the solvent was carefully decanted

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

Procedure: The procedure described in Example 3, step 3.4. is followed. Starting from 3.00 g (15.13 mmol) of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate, 2.58 g (15.13 mmol) of ethyl 5-hydroxymethyl-isoxazole-3-carboxylate, 5.27 ml (30.26 mmol) of N,N-diisopropylethylamine and 3.05 g (15.13 mmol) of para-nitrophenyl chloroformate, 4.50 g of product are obtained in the form of a colourless oil (75%).

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (7.3 g, 25.3 mmol) and triethylorothoformate (24 mL, 152 mmol) in acetic acid (200 mL) was added sodium azide (9.9 g, 152 mmol) and the resulting mixture was set under inert atmosphere. The mixture was heated at 100° C. for 4 h and then cooled to RT at which time the volatiles were removed in vacuo. The residue was taken up in ethyl acetate (200 mL) and washed with aqueous sodium bicarbonate solution, followed by brine. The organics were dried over sodium sulfate, filtered, and concentrate to dryness under vacuum. The residue was placed in the refrigerator overnight and the next day a solid white precipitate was observed. The precipitate was triturated with hexane and the solvent was carefully decanted to give the title compound 3.2 g (50.3%) as a white solid. ESI-MS calculated for C11H17N5O2: Exact Mass: 251.28. Found 252.28. cooled to RT at which time the volatiles were removed in vacuo washed with aqueous sodium bicarbonate solution The organics were dried over sodium sulfate filtered concentrate to dryness under vacuum was placed in the refrigerator overnight The precipitate was triturated with hexane the solvent was carefully decanted

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (7.3 g, 25.3 mmol) and triethylorothoformate (24 mL, 152 mmol) in acetic acid (200 mL) was added sodium azide (9.9 g, 152 mmol) and the resulting mixture was set under inert atmosphere. The mixture was heated at 100° C. for 4 h and then cooled to RT at which time the volatiles were removed in vacuo. The residue was taken up in ethyl acetate (200 mL) and washed with aqueous sodium bicarbonate solution, followed by brine. The organics were dried over sodium sulfate, filtered, and concentrate to dryness under vacuum. The residue was placed in the refrigerator overnight and the next day a solid white precipitate was observed. The precipitate was triturated with hexane and the solvent was carefully decanted to give the title compound 3.2 g (50.3%) as a white solid. ESI-MS calculated for C11H17N5O2: Exact Mass: 251.28. Found 252.28. cooled to RT at which time the volatiles were removed in vacuo washed with aqueous sodium bicarbonate solution The organics were dried over sodium sulfate filtered concentrate to dryness under vacuum was placed in the refrigerator overnight The precipitate was triturated with hexane the solvent was carefully decanted

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (7.3 g, 25.3 mmol) and triethylorthoformate (24 mL, 152 mmol) in acetic acid (200 mL) was added sodium azide (9.9 g, 152 mmol) and the resulting mixture was set under inert atmosphere. The mixture was heated at 100° C. for 4 h and then cooled to RT at which time the volatiles were removed in vacuo. The residue was taken up in ethyl acetate (200 mL) and washed with aqueous sodium bicarbonate solution, followed by brine. The organics were dried over sodium sulfate, filtered, and concentrate to dryness under vacuum. The residue was placed in the refrigerator overnight and the next day a solid white precipitate was observed. The precipitate was triturated with hexane and the solvent was carefully decanted to give the title compound 3.2 g (50.3%) as a white solid. ESI-MS calculated for C11H17N5O2: Exact Mass: 251.28. Found 252.28. cooled to RT at which time the volatiles were removed in vacuo washed with aqueous sodium bicarbonate solution The organics were dried over sodium sulfate filtered concentrate to dryness under vacuum was placed in the refrigerator overnight The precipitate was triturated with hexane the solvent was carefully decanted

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

Procedure: tert-Butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (1 g, 1.0 eq.) was added to a solution of sodium bicarbonate (0.84 g, 2.0 eq.) in water (5 ml) at 5° C. FMOC—Cl (1.56 g, 1.2 eq.) in 1,4-dioxane (10 ml) was added dropwise. The reaction mixture was stirred at room temperature for 3 h, transferred into iced water (50 mL), and extracted with EtOAc (2×100 mL). The combined organic layers was washed with brine (2×50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford 1.9 g of tert-butyl 6-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-azabicyclo[3.1.0]hexane-3-carboxylate (yield 90%). extracted with EtOAc (2×100 mL) The combined organic layers was washed with brine (2×50 mL) dried over Na2SO4 filtered concentrated under reduced pressure (25° C., 20 mmHg)

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.250 g, 1.0 eq.) was dissolved in DCM (12 mL). tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate (0.17 g, 1.2 eq.) was added and the reaction mixture was cooled to −60° C. T3P (0.51 mL, 1.2 eq.), followed by DIPEA (0.24 mL, 2.0 eq.) was then added at the same temperature. The reaction mixture was stirred for 30 min. and transferred into water (50 mL) and extracted with DCM (2×50 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford crude product, which was purified by chromatography (0-5% MeOH in DCM) to give (Z)-tert-butyl 6-(3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylamido)-3-azabicyclo[3.1.0]hexane-3-carboxylate (0.28 g; 66.1% yield). was then added at the same temperature extracted with DCM (2×50 mL) The combined organic layer was washed with brine (50 mL) dried over anhydrous MgSO4 filtered concentrated under reduced pressure (25° C., 20 mmHg) to afford crude product, which was purified by chromatography (0-5% MeOH in DCM)

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

Procedure: The procedure described in Example 3, step 3.4. is followed. Starting from 3.00 g (15.13 mmol) of tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate, 2.58 g (15.13 mmol) of ethyl 5-hydroxymethyl-isoxazole-3-carboxylate, 5.27 ml (30.26 mmol) of N,N-diisopropylethylamine and 3.05 g (15.13 mmol) of para-nitrophenyl chloroformate, 4.50 g of product are obtained in the form of a colourless oil (75%).