azepan-1-amine

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: To 101 (6.03 g, 20.0 mmol) dissolved in acetone (75 mL) was added a solution of 1-aminohomopiperidine (2.3 mL, 20.0 mmol) in acetone (10 mL) followed by addition of NaOH (8.0 mL 2.5 N NaOH solution, 20.0 mmol) and 20 mL of water. The reaction mixture was allowed to stir at reflux overnight under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated on a rotary evaporator and the resulting oil was dried overnight under vacuum. Column chromatography (96:3:1 dichloromethane: methanol: conc. ammonium hydroxide) yielded a light purple solid 152 (1.2 g, 16%), mp 139° C.; TLC (silica gel, 96:3:1, CH2Cl2, CH3OH, conc. NH4OH), Rf 0.31; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 52.5 min, 94.9% purity; MS (ESI): m/z 383 (M+H, 100). at reflux overnight under nitrogen The reaction mixture was extracted 3 times with dichloromethane the combined organic layers were washed with brine dried over potassium carbonate The sample was concentrated on a rotary evaporator the resulting oil was dried overnight under vacuum

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

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

Procedure: To 101 (6.03 g, 20.0 mmol) dissolved in acetone (75 mL) was added a solution of 1-aminohomopiperidine (2.3 mL, 20.0 mmol) in acetone (10 mL) followed by addition of NAOH (8.0 mL 2.5 N NaOH solution, 20.0 mmol) and 20 mL of water. The reaction mixture was allowed to stir at reflux overnight under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated on a rotary evaporator and the resulting oil was dried overnight under vacuum. Column chromatography (96:3:1 dichloromethane:methanol:conc. ammonium hydroxide) yielded a light purple solid 152 (1.2 g, 16%), mp 139° C.; TLC (silica gel, 96:3:1, CH2Cl2, CH3OH, conc. NH4OH), Rf 0.3 1; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2): CH3OH:CH3CN], 264 nm, Rt 52.5 min, 94.9% purity; MS (ESI): m/z 383 (M+H, 100). at reflux overnight under nitrogen The reaction mixture was extracted 3 times with dichloromethane the combined organic layers were washed with brine dried over potassium carbonate The sample was concentrated on a rotary evaporator the resulting oil was dried overnight under vacuum

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

Procedure: To 101 (6.03 g, 20.0 mmol) dissolved in acetone (75 mL) was added a solution of 1-aminohomopiperidine (2.3 mL, 20.0 mmol) in acetone (10 mL) followed by addition of NaOH (8.0 mL 2.5 N NaOH solution, 20.0 mmol) and 20 mL of water. The reaction mixture was allowed to stir at reflux overnight under nitrogen. The reaction mixture was extracted 3 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was concentrated on a rotary evaporator and the resulting oil was dried overnight under vacuum. Column chromatography (96:3:1 dichloromethane:methanol:conc. ammonium hydroxide) yielded a light purple solid 152 (1.2 g, 16%), mp 139° C.; TLC (silica gel, 96:3:1, CH2Cl2, CH3OH, conc. NH4OH), Rf 0.31; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 52.5 min, 94.9% purity; MS (ESI): m/z 383 (M+H, 100). at reflux overnight under nitrogen The reaction mixture was extracted 3 times with dichloromethane the combined organic layers were washed with brine dried over potassium carbonate The sample was concentrated on a rotary evaporator the resulting oil was dried overnight under vacuum

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (43 mg, yield 55%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 10 min with heating under reflux for 3 hr the reaction the reaction solution was then extracted with chloroform by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (43 mg, yield 55%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 10 min with heating under reflux for 3 hr the reaction the reaction solution was then extracted with chloroform by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 47%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 10 min with heating under reflux for 3 hr the reaction the reaction solution was then extracted with chloroform by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC