1-[3-(4-bromophenyl)propyl]pyrrolidine

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 1.03 g (4.82 mmol) 3-(4-bromo-phenyl)-propionaldehyde and 0.41 mL (4.82 mmol) pyrrolidine in 50 mL MeOH is adjusted to pH 4-5 with glacial acetic acid. Then 400 mg (6.05 mmol) NaBH3CN are added batchwise and the reaction is stirred for 3 days at RT. The reaction solution is diluted with 30 mL water and the aqueous phase is extracted with 50 mL EtOAc. The organic phase is dried over Na2SO4 and the solvent is eliminated i.vac. Further purification is carried out by column chromatography on silica gel (EtOAc/MeOH/NH3 9:1:0.1). the aqueous phase is extracted with 50 mL EtOAc The organic phase is dried over Na2SO4 Further purification

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

Procedure: A mixture of 5-nitro-pyrimidin-2-ylamine (0.15 g, 1.1 mmol), intermediate 51 (Example 101) (0.30 g, 1.1 mmol), Pd2(dba)2 (75 mg, 0.082 mmol), Xantphos (96 mg, 0.17 mmol) and cesium carbonate (0.69 g, 2.1 mmol) was suspended in dioxane (15 mL) and heated at reflux under the argon atmosphere for 15 h. The mixture was allowed to cool to room temperature, filtered and washed with DCM. The filtrate was concentrated and the residue purified by flash chromatography on silica gel (10% MeOH/DCM to 20% MeOH and 2% TEA/DCM) to afford the title compound as a yellow solid (0.20 g, 56%). heated at reflux under the argon atmosphere for 15 h filtered washed with DCM The filtrate was concentrated the residue purified by flash chromatography on silica gel (10% MeOH/DCM to 20% MeOH and 2% TEA/DCM)

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

Procedure: To a solution of intermediate 50 (Example 100) (3.5 g, 13 mmol) in dioxane (40 mL) was added pyrrolidine (2.1 mL, 25 mmol), followed by cesium carbonate (8.2 g, 25 mmol). The mixture was stirred at room temperature for 15 h and poured into water. The mixture was extracted with ethyl acetate and the organic layer separated, washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the residue purified by flash chromatography on silica gel (10% MeOH/DCM to 25% MeOH and 2% TEA/DCM) to afford the title compound (1.8 g, 53%) as a pale orange oil. The mixture was extracted with ethyl acetate the organic layer separated washed with brine dried over Na2SO4 filtered The filtrate was concentrated the residue purified by flash chromatography on silica gel (10% MeOH/DCM to 25% MeOH and 2% TEA/DCM)