methyl (2S)-1-chlorosulfonylpyrrolidine-2-carboxylate

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

Procedure: The product of Example 205 (0.030 g, 0.0703 mmol) in acetonitrile (2 ml) was treated with the product of Example 461A (0.018 g, 0.077 mmol) and triethylamine (0.011 ml, 0.077 mmol), stirred at 60° C. for 20 hours and cooled to about 25° C. The solvent was evaporated under reduced pressure, and the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/10 mM ammonium acetate in water over 8 minutes (10 minutes run time) at a flow rate of 40 mL/min give the title compound (7 mg, 16%). 1H NMR (300 MHz, DMSO-d6) δ 0.99 (d, J=6.25 Hz, 6 H) 1.59 (m, 2 H) 1.67 (m, 2 H) 1.87 (m, 4 H) 2.09 (d, J=8.46 Hz, 1 H) 3.60 (s, 3 H) 4.26 (dd, J=8.64, 3.86 Hz, 1 H) 4.50 (m, 2 H) 7.55 (m, 4 H) 7.73 (d, J=8.82 Hz, 1 H) 8.57 (dd, J=8.09, 1.84 Hz, 1 H) 8.90 (dd, J=4.78, 1.84 Hz, 1 H) 10.53 (s, 1 H) 14.07 (s, 1 H). MS (ESI−) m/z 617 (M−H)−. cooled to about 25° C The solvent was evaporated under reduced pressure the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) over 8 minutes (10 minutes run time)

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

Procedure: The product of Example 205 (0.030 g, 0.0703 mmol) in acetonitrile (2 ml) was treated with the product of Example 461A (0.018 g, 0.077 mmol) and triethylamine (0.011 ml, 0.077 mmol), stirred at 60° C. for 20 hours and cooled to about 25° C. The solvent was evaporated under reduced pressure, and the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/10 mM ammonium acetate in water over 8 minutes (10 minutes run time) at a flow rate of 40 mL/min give the title compound (7 mg, 16%). 1H NMR (300 MHz, DMSO-d6) δ 0.99 (d, J=6.25 Hz, 6 H) 1.59 (m, 2 H) 1.67 (m, 2 H) 1.87 (m, 4 H) 2.09 (d, J=8.46 Hz, 1 H) 3.60 (s, 3 H) 4.26 (dd, J=8.64, 3.86 Hz, 1 H) 4.50 (m, 2 H) 7.55 (m, 4 H) 7.73 (d, J=8.82 Hz, 1 H) 8.57 (dd, J=8.09, 1.84 Hz, 1 H) 8.90 (dd, J=4.78, 1.84 Hz, 1 H) 10.53 (s, 1 H) 14.07 (s, 1 H). MS (ESI−) m/z 617 (M−H)−. cooled to about 25° C The solvent was evaporated under reduced pressure the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) over 8 minutes (10 minutes run time)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of L-proline methyl ester hydrochloride (0.33 g, 0.002 mole) in toluene (5 ml), dichloromethane (2 ml) and triethylamine (0.6 ml, 0.004 mole) was added dropwise over a period of 3 minutes to a cold (−20° C.) solution of sulfuryl chloride (0.32 ml, 0.0039 mole) in toluene. The mixture was stirred an additional 45 minutes at −20° C. The reaction was filtered and the solvent was removed under reduced pressure to give the title compound (0.40 g). 1H NMR (300 MHz, CDCl3) δ 2.13 (m, 2 H) 2.32 (m, 2 H) 3.58 (m, 1 H) 3.75 (m, 1 H) 3.79 (s, 3 H) 4.40 (dd, J=8.82, 4.04 Hz, 1 H). The reaction was filtered the solvent was removed under reduced pressure

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

Procedure: The product of Example 205 (0.030 g, 0.0703 mmol) in acetonitrile (2 ml) was treated with the product of Example 461A (0.018 g, 0.077 mmol) and triethylamine (0.011 ml, 0.077 mmol), stirred at 60° C. for 20 hours and cooled to about 25° C. The solvent was evaporated under reduced pressure, and the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/10 mM ammonium acetate in water over 8 minutes (10 minutes run time) at a flow rate of 40 mL/min give the title compound (7 mg, 16%). 1H NMR (300 MHz, DMSO-d6) δ 0.99 (d, J=6.25 Hz, 6 H) 1.59 (m, 2 H) 1.67 (m, 2 H) 1.87 (m, 4 H) 2.09 (d, J=8.46 Hz, 1 H) 3.60 (s, 3 H) 4.26 (dd, J=8.64, 3.86 Hz, 1 H) 4.50 (m, 2 H) 7.55 (m, 4 H) 7.73 (d, J=8.82 Hz, 1 H) 8.57 (dd, J=8.09, 1.84 Hz, 1 H) 8.90 (dd, J=4.78, 1.84 Hz, 1 H) 10.53 (s, 1 H) 14.07 (s, 1 H). MS (ESI−) m/z 617 (M−H)−. cooled to about 25° C The solvent was evaporated under reduced pressure the residue was purified by reverse phase preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) over 8 minutes (10 minutes run time)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of L-proline methyl ester hydrochloride (0.33 g, 0.002 mole) in toluene (5 ml), dichloromethane (2 ml) and triethylamine (0.6 ml, 0.004 mole) was added dropwise over a period of 3 minutes to a cold (−20° C.) solution of sulfuryl chloride (0.32 ml, 0.0039 mole) in toluene. The mixture was stirred an additional 45 minutes at −20° C. The reaction was filtered and the solvent was removed under reduced pressure to give the title compound (0.40 g). 1H NMR (300 MHz, CDCl3) δ 2.13 (m, 2 H) 2.32 (m, 2 H) 3.58 (m, 1 H) 3.75 (m, 1 H) 3.79 (s, 3 H) 4.40 (dd, J=8.82, 4.04 Hz, 1 H). The reaction was filtered the solvent was removed under reduced pressure