3-azabicyclo[3.2.2]nonane

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

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

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

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

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

Procedure: To a solution of 2-fluoro-3-cyanopyridine (0.4 g, 3.27 mmol) in 30 mL tetrahydrofuran was added triethylamine (0.66 g, 6.5 mmol) and 3-aza-bicyclo[3.2.2]nonane (0.5 g, 3.9 mmol). The reaction was held at 50° C. for 12 hours, cooled and diluted with 100 mL ethyl acetate. The organics were washed with water (2×50 mL), brine (1×50 mL), dried (MgSO4) and concentrated. Column chromatography (20% ethyl acetate/hexanes) gave the title compound as a solid. MS (ESI/NH3) m/z 126 (M+H)+ cooled The organics were washed with water (2×50 mL), brine (1×50 mL) dried (MgSO4) concentrated

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

Procedure: To a solution of 2-fluoro-3-cyanopyridine (0.4 g, 3.27 mmol) in 30 mL tetrahydrofuran was added triethylamine (0.66 g, 6.5 mmol) and 3-aza-bicyclo[3.2.2]nonane (0.5 g, 3.9 mmol). The reaction was held at 50° C. for 12 hours, cooled and diluted with 100 mL ethyl acetate. The organics were washed with water (2×50 mL), brine (1×50 mL), dried (MgSO4) and concentrated. Column chromatography (20% ethyl acetate/hexanes) gave the title compound as a solid. MS (ESI/NH3) m/z 126 (M+H)+ cooled The organics were washed with water (2×50 mL), brine (1×50 mL) dried (MgSO4) concentrated

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

Procedure: To a solution of 3-azabicyclo[3.2.2]nonane (1.25 g) in dichioromethane (20 ml) and water (0.75 ml) was added dropwise a solution of bromoacetyl bromide (2.02 g) in dichloromethane (10 ml) at, 5°-10° C. The mixture was allowed to warm to room temperature and stirred for 1 hour at the same temperature. The reaction mixture was washed with a saturated sodium bicarbonate aqueous solution (10 ml) and a brine (10 ml). The organic layer was dried over magnesium sulfate. Filtration and evaporation gave N-bromomethylcarbonyl-3-azabicyclo[3.2.2]nonane (1.15 g). The compound was used in a following reaction step without further purification. The reaction mixture was washed with a saturated sodium bicarbonate aqueous solution (10 ml) The organic layer was dried over magnesium sulfate Filtration and evaporation

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

Procedure: 4-Acetoxy-2-naphthalenesulfonyl chloride (861 mg, 3.02 mmol) and 3-azabicyclo[3.2.2]nonane (379 mg, 3.02 mmol) were combined in CHCl3 (20 ml) and pyridine (20 ml) and the mixture was stirred at room temperature for 15 hr. At this time the solvent was evaporated under reduced pressure and the residue was partitioned between EtOAc and 1N aq HCl. The EtOAc was then washed with saturated aq NaHCO3, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography using 1% acetone in CHCl3 to provide the pure product as a white foam (712 mg, 63% yield): 1H NMR (CDCl3) δ 1.52-1.84 (8H, m, 4×CH2), 2.02-2.13 (2H, br s, 2×CH), 2.46 (3H, s, CH3CO), 3.31 (4H, d, J=4.2 Hz, 2×CH2), 7.56-7.71 (3H, m, ArH), 7.92-8.02 (2H, m, ArH). At this time the solvent was evaporated under reduced pressure the residue was partitioned between EtOAc and 1N aq HCl The EtOAc was then washed with saturated aq NaHCO3 dried over Na2SO4 concentrated The residue was purified by flash chromatography

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

Procedure: The title compound was prepared by reacting 4-methyl-1-naphthalenesulfonyl chloride (0.69 g) with 3-azabicyclo[3.2.2]nonane (0.43 g) in the presence of DIEA using a procedure similar to that of Example 5. Yield 1.00 g of a grey solid, mp: 143.3°-147.2° C.

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

Procedure: The title compound was prepared by reacting 4-methyl-1-naphthalenesulfonyl chloride (0.69 g) with 3-azabicyclo[3.2.2]nonane (0.43 g) in the presence of DIEA using a procedure similar to that of Example 5. Yield 1.00 g of a grey solid, mp: 143.3°-147.2° C.

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

Procedure: The title compound was prepared by reacting 4-methoxy-1-naphthalenesulfonyl chloride (0.27 g) with 3-azabicyclo[3.2.2]nonane (0.16 g) in the presence of DIEA (0.30 g) using a procedure similar to that of Example 5. Yield: 0.34 g of a white solid, mp: 136.2°-138.6° C.

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

Procedure: The title compound was prepared by reacting 4-methoxy-1-naphthalenesulfonyl chloride (0.25 g) with 3-azabicyclo[3.2.2]nonane (0.12 g) in the presence of DIEA (0.16 g) using a procedure similar to that used in Example 5. Yield: 0.24 g, mp 167.7°-169.5° C. (soften 166.1° C.). Yield: 0.24 g, mp 167.7°-169.5° C. (soften 166.1° C.)