3-(3-bromopropyl)-1,3-oxazolidin-2-one

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

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

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

Procedure: To a cooled solution (15-20° C.) of 1,3-dibromopropane (6.4 mL, 63.05 mmol) in dry DMSO (5 mL) was added ground KOH (0.920 g, 16.40 mmol). 2-Oxazolidinone (1.100 g, 12.63 mmol) was added in small amounts over 5 min, and the reaction was stirred for 4 hr at 20° C. The mixture was diluted with ether (100 mL) and H2O (20 mL), and the aqueous phase was extracted with ether (3×50 mL). After drying with MgSO4, the crude product was purified by flash chromatography using a step gradient (25% EtOAc/75% hexanes to 50% EtOAc/50% hexanes) to give N-(3′-bromopropyl)-2-oxazolidinone, 17 (1.48 g, 56%). IR (neat) 1747 cm−1; 1H NMR (CDCl3) δ 4.30 (2H, t, J=7.2 Hz), 3.57 (2H, t, J=8.2 Hz), 3.33-3.43 (4H, q), 2.03-2.17 (2H, m); 13C NMR (CDCl3) δ 158.4, 61.7, 45.0, 43.0, 30.4, 29.9; HRMS (FAB+) m/z: calcd for C6H10NO2Br, 207.9972; found, 207.9957. the aqueous phase was extracted with ether (3×50 mL) After drying with MgSO4 the crude product was purified by flash chromatography

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

Procedure: To a cooled solution (15-20° C.) of 1,3-dibromopropane (6.4 mL, 63.05 mmol) in dry DMSO (5 mL) was added ground KOH (0.920 g, 16.40 mmol). 2-Oxazolidinone (1.100 g, 12.63 mmol) was added in small amounts over 5 min, and the reaction was stirred for 4 hr at 20° C. The mixture was diluted with ether (100 mL) and H2O (20 mL), and the aqueous phase was extracted with ether (3×50 mL). After drying with MgSO4, the crude product was purified by flash chromatography using a step gradient (25% EtOAc/75% hexanes to 50% EtOAc/50% hexanes) to give N-(3′-bromopropyl)-2-oxazolidinone, 17 (1.48 g, 56%). IR (neat) 1747 cm−1; 1H NMR (CDCl3) δ 4.30 (2H, t, J=7.2 Hz), 3.57 (2H, t, J=8.2 Hz), 3.33-3.43 (4H, q), 2.03-2.17 (2H, m); 13C NMR (CDCl3) δ 158.4, 61.7, 45.0, 43.0, 30.4, 29.9; HRMS (FAB+) m/z: calcd for C6H10NO2Br, 207.9972; found, 207.9957. the aqueous phase was extracted with ether (3×50 mL) After drying with MgSO4 the crude product was purified by flash chromatography

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

Procedure: To a stirred solution of 7-nitro-6-(4-o-tolyl-piperazin-1-yl)-2H-isoquinolin-1-one (0.25 g, 0.68 mmol) in anhydrous DMF (10 mL), 3-(3-bromo-propyl)-oxazolidin-2-one (0.14 g, 0.68 mmol) was added followed by potassium bis(trimethylsilyl) amide (0.27 g, 1.37 mmol) at 0° C. under N2 atmosphere. The reaction mass allowed to stir at room temperature for 6 h. The progress of the reaction was monitored by LCMS analysis. Upon completion of the reaction, solvent was removed in vacuo. Residue obtained was quenched with water, and extracted in dichloromethane (3×75 mL). The combined extract was washed with water, brine solution and dried over anhydrous Na2SO4. The crude product obtained was purified by the flash column chromatography (230-400 size mesh) using 1.5-1.75% methanol in dichloromethane to afford the compound 7-nitro-2-[3-(2-oxo-oxazolidin-3-yl)-propyl]-6-(4-o-tolyl-piperazin-1-yl)-2H-isoquinolin-1-one. Yield (0.25 g, 75%; and off-color solid). Upon completion of the reaction, solvent was removed in vacuo Residue obtained was quenched with water extracted in dichloromethane (3×75 mL) The combined extract was washed with water, brine solution dried over anhydrous Na2SO4 The crude product obtained was purified by the flash column chromatography (230-400 size mesh)

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