(4-phenylpyrrolidin-3-yl)methanol

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:

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: A solution of (4-phenylpyrrolidin-3-yl)methanol (7 mg, 0.033 mmol), TBTU (13 mg, 0.039 mmol, 1.2 equ.) and N-ethyl-N-isopropylpropan-2-amine (11 μL, 0.066 mmol, 2 equ.) in DMF (0.3 mL) was added to 5-pyridin-2-ylisoxazole-4-carboxylic acid (6 mg, 0.033 mmol) and the reaction mixture was stirred at rt for 2 h. The solvent was evaporated and the crude product was purified by RP-HPLC. After evaporation of the solvents from the pure fractions, the residue was dissolved in chloroform and washed with diluted NaOH to provide the neutral compound in the organic phase that was dried (Na2SO4) and evaporated and dried in vacuum to yield the title compound (3 mg). MS (ESI, pos. ion) m/z calcd for C20H19N3O3: 349.1426, found 349.1427. The solvent was evaporated the crude product was purified by RP-HPLC After evaporation of the solvents from the pure fractions the residue was dissolved in chloroform washed with diluted NaOH to provide the neutral compound in the organic phase that was dried (Na2SO4) evaporated dried in vacuum

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

Procedure: A solution of (4-phenylpyrrolidin-3-yl)methanol (7 mg, 0.033 mmol), TBTU (13 mg, 0.039 mmol, 1.2 equ.) and N-ethyl-N-isopropylpropan-2-amine (11 μL, 0.066 mmol, 2 equ.) in DMF (0.3 mL) was added to 5-(4-methylphenyl)isoxazole-4-carboxylic acid (7 mg, 0.033 mmol) and the reaction mixture was stirred at rt for 2 h. The solvent was evaporated and the crude product was purified by RP-HPLC. After evaporation of the solvents the product was dried in vacuum to yield the title compound (4 mg). MS (ESI, pos. ion) m/z calcd for C22H22N2O3: 362.1630, found 362.1629. The solvent was evaporated the crude product was purified by RP-HPLC After evaporation of the solvents the product was dried in vacuum

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

Procedure: A solution of (4-phenylpyrrolidin-3-yl)methanol (7 mg, 0.033 mmol), TBTU (13 mg, 0.039 mmol, 1.2 equ.) and N-ethyl-N-isopropylpropan-2-amine (11 μL, 0.066 mmol, 2 equ.) in DMF (0.3 mL) was added to 3-(4-methylphenyl)isoxazole-4-carboxylic acid (7 mg, 0.033 mmol) and the reaction mixture was stirred at rt for 2 h. The solvent was evaporated and the crude product was purified by RP-HPLC. After evaporation of the solvents the product was dried in vacuum to yield the title compound (5 mg). MS (ESI, pos. ion) m/z calcd for C22H22N2O3: 362.1630, found 362.1624. The solvent was evaporated the crude product was purified by RP-HPLC After evaporation of the solvents the product was dried in vacuum

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

Procedure: A solution of 196 mg (1.1 mmol) of 3-(SR)-hydroxymethyl-4-(SR)-phenylpyrrolidine (from Example 1, Step C) and 27 mg (0.2 mmol) of 4-(N,N-dimethylamino)pyridine in 5 mL of pyridine at 0 ° C. was treated with 488 mg (2.8 mmol) of benzenesulfonyl chloride. The cooling bath was removed and the resulting mixture was stirred at rt for 1 h. The reaction mixture was treated with an additional 290 mg of benzenesulfonyl chloride and the resulting mixture was stirred at rt for 1 h. The reaction mixture was partitioned between 50 mL of ether and 20 mL of sat'd CuSO4 and the layers were separated. The organic layer was washed with 30 mL of H2O, 30 mL of sat'd NaCl, dried over MgSO4 and concentrated in vacuo. Flash chromatography on 30 g of silica gel using3:2 v/v hexanes/ether afforded 340 mg (67%) of the title compound as a solid. 1H NMR (500 MHz, CDCl3): δ2.65-2.72 (m, 1H), 3.21 (dd, J=7.8, 10.3, 1H), 3.44-3.67 (6H), 6.94-7.90 (15H). Mass Spectrum (NH3-CI): m/z 458 (M+1). The cooling bath was removed The reaction mixture was treated with an additional 290 mg of benzenesulfonyl chloride the resulting mixture was stirred at rt for 1 h The reaction mixture was partitioned between 50 mL of ether and 20 mL of sat'd CuSO4 the layers were separated The organic layer was washed with 30 mL of H2O, 30 mL of sat'd NaCl dried over MgSO4 concentrated in vacuo