4-bromopiperidine;hydrobromide

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

Procedure: Benzoyl chloride (1.41 g) was added to a solution of 4-bromopiperidine hydrobromide (2.45 g) in THF (30 ml) at 0° C., followed by triethylamine (2.2 g, 2.2 eq). The solution was stirred at room temperature for 1 h, and evaporated and. The residue was dissolved in dichloromethane (100 ml), washed with water, 1M HCl and saturated sodium bicarbonate, dried and evaporated to give the title compound as colourless oil (2.76 g, 100%). evaporated The residue was dissolved in dichloromethane (100 ml) washed with water, 1M HCl and saturated sodium bicarbonate dried evaporated

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

Procedure: Benzoyl chloride (1.41 g) was added to a solution of 4-bromopiperidine hydrobromide (2.45 g) in THF (30 ml) at 0° C., followed by triethylamine (2.2 g, 2.2 eq). The solution was stirred at room temperature for 1 h, and evaporated and. The residue was dissolved in dichloromethane (100 ml), washed with water, 1M HCl and saturated sodium bicarbonate, dried and evaporated to give the title compound as colourless oil (2.76 g, 100%). evaporated The residue was dissolved in dichloromethane (100 ml) washed with water, 1M HCl and saturated sodium bicarbonate dried evaporated

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

Procedure: Benzoyl chloride (1.41 g) was added to a solution of 4-bromopiperidine hydrobromide (2.45 g) in THF (30 ml) at 0° C., followed by triethylamine (2.2 g, 2.2 eq). The solution was stirred at room temperature for 1 h, and evaporated and. The residue was dissolved in dichloromethane (100 ml), washed with water, 1M HCl and saturated sodium bicarbonate, dried and evaporated to give the title compound as colourless oil (2.76 g, 100%). evaporated The residue was dissolved in dichloromethane (100 ml) washed with water, 1M HCl and saturated sodium bicarbonate dried evaporated

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

Procedure: In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (42.7 mg, 0.104 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with 4-bromopiperidine hydrobromide (105 mg, 0.428 mmol), acetic acid (0.120 mL, 2.10 mmol) and sodium triacetoxyborohydride (51.1 mg, 0.241 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinone (77.3 mg). The mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (42.7 mg, 0.104 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with 4-bromopiperidine hydrobromide (105 mg, 0.428 mmol), acetic acid (0.120 mL, 2.10 mmol) and sodium triacetoxyborohydride (51.1 mg, 0.241 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinone (77.3 mg). The mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure

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

Procedure: Benzoyl chloride (1.41 g) was added to a solution of 4-bromopiperidine hydrobromide (2.45 g) in THF (30 ml) at 0° C., followed by triethylamine (2.2 g, 2.2 eq). The solution was stirred at room temperature for 1 h, and evaporated and. The residue was dissolved in dichloromethane (100 ml), washed with water, 1M HCl and saturated sodium bicarbonate, dried and evaporated to give the title compound as colourless oil (2.76 g, 100%). evaporated The residue was dissolved in dichloromethane (100 ml) washed with water, 1M HCl and saturated sodium bicarbonate dried evaporated

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

Procedure: To a solution of 4-bromopiperidine hydrobromide (3.0 g, 12.2 mmol) in tetrahydrofuran (30 ml) were added 1-{[(benzyloxy)carbonyl]oxy}-2,5-pyrrolidinedione (3.20 g, 12.9 mmol), N-methylmorpholine (1.62 ml, 14.7 mmol) and 4-N,N-dimethylaminopyridine (30 mg) at room temperature, and stirred at room temperature for 16 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a 1N-aqueous hydrochloric acid solution, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=1/1) to obtain benzyl 4-bromo-1-piperidinecarboxylate (3.58 g, 98%). extracted with ethyl acetate The organic layer was washed with a 1N-aqueous hydrochloric acid solution dried over anhydrous magnesium sulfate distilled under reduced pressure to remove the solvent the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=1/1)

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

Procedure: Benzoyl chloride (1.41 g) was added to a solution of 4-bromopiperidine hydrobromide (2.45 g) in THF (30 ml) at 0° C., followed by triethylamine (2.2 g, 2.2 eq). The solution was stirred at room temperature for 1 h, and evaporated and. The residue was dissolved in dichloromethane (100 ml), washed with water, 1M HCl and saturated sodium bicarbonate, dried and evaporated to give the title compound as colourless oil (2.76 g, 100%). evaporated The residue was dissolved in dichloromethane (100 ml) washed with water, 1M HCl and saturated sodium bicarbonate dried evaporated

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

Procedure: In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (42.7 mg, 0.104 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with 4-bromopiperidine hydrobromide (105 mg, 0.428 mmol), acetic acid (0.120 mL, 2.10 mmol) and sodium triacetoxyborohydride (51.1 mg, 0.241 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinone (77.3 mg). The mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure