3-(2-methylpiperidin-1-yl)propan-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:; See reaction.notes.procedure_details.

Procedure: 65 mg (52%) of the target compound was obtained in the same manner of Example 1, using 3-(4-chloro-benzyl)-2,4-dioxoquinazoline-7-carboxylic acid (90 mg, 0.272 mol) obtained in Example 1 and 3-(2-methyl-piperidine-1-yl)-propylamine (103 mL, 0.598 mmol).

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

Procedure: To a solution of 1-(3-aminopropyl)-2-pipecoline (1.00 g, 6.40 mmole) in methylene chloride (25 mL) was added palmitoyl chloride (1.73 g, 6.40 mmole) in small portions. The reaction mixture was stirred at room temperature overnight. The reaction mixture was washed twice with saturated aqueous sodium bicarbonate and once with brine. The organic layer was dried over magnesium sulfate and the salts removed by filtration. The solvent was removed under reduced pressure and the residue dried in vacuo to give the title compound (2.12 g, 83%), mp. 48°-50° C. 1H NMR (300 MHz, CDCl3): δ0.883 (3H, t, J=6.5 Hz), 1.136 (3H, d, J=5.5 Hz), 1.254 (24H, bs), 1.60 to 1.70 (4H, m), 2.157 (2H, t, J=7.6 Hz), 2.37 to 2.39 (2H, m), 2.89 to 2.94 (3H, m), 3.24 to 3.27 (1H, m), 3.40 to 3.44 (1H, m), and 7.266 (1H, bs). Analysis calculated for C25H50N2O.1/4H2O C, 75.16; H, 12.61; N, 7.01. Found: C, 75.16; H, 12.69; N, 7.16. The reaction mixture was washed twice with saturated aqueous sodium bicarbonate and once with brine The organic layer was dried over magnesium sulfate the salts removed by filtration The solvent was removed under reduced pressure the residue dried in vacuo

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

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-2-methylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, 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 (46 mg, yield 56%). the mixture was further stirred at room temperature for 16 hr 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]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-2-methylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, 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 (46 mg, yield 56%). the mixture was further stirred at room temperature for 16 hr 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]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-2-methylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, 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 (39 mg, yield 47%). the mixture was further stirred at room temperature for 15 hr 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: The title compound, as a TFA salt, was prepared in a manner similar to Example 74 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 3-(2-methylpiperidin-1-yl)propan-1-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.32 (m, 3 H) 1.38-1.55 (m, 2 H) 1.56-1.74 (m, 2 H) 1.74-2.06 (m, 4 H) 2.40-2.47 (m, 3 H) 2.91-3.16 (m, 2 H) 3.16-3.34 (m, 2 H) 3.35-3.69 (m, 3 H) 7.63-7.70 (m, 1 H) 7.72-7.86 (m, 2H) 8.20 (br. s., 1 H) 8.42 (d, J=7.33 Hz, 2 H) 8.85-9.00 (m, 2 H) 9.03-9.38 (m, 1 H) 12.63-13.81 (m, 1 H). MS m/z [M+H]+ 459.2.

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

Procedure: The title compound, as a TFA salt, was prepared in a manner similar to Example 74 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 3-(2-methylpiperidin-1-yl)propan-1-amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.32 (m, 3 H) 1.38-1.55 (m, 2 H) 1.56-1.74 (m, 2 H) 1.74-2.06 (m, 4 H) 2.40-2.47 (m, 3 H) 2.91-3.16 (m, 2 H) 3.16-3.34 (m, 2 H) 3.35-3.69 (m, 3 H) 7.63-7.70 (m, 1 H) 7.72-7.86 (m, 2H) 8.20 (br. s., 1 H) 8.42 (d, J=7.33 Hz, 2 H) 8.85-9.00 (m, 2 H) 9.03-9.38 (m, 1 H) 12.63-13.81 (m, 1 H). MS m/z [M+H]+ 459.2.

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

Procedure: The title compound, as a TFA salt, was prepared in a manner similar to Example 74 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and 3-(2-methylpiperidin-1-yl)propan-1-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.32 (m, 3H) 1.38-1.55 (m, 2H) 1.56-1.74 (m, 2H) 1.74-2.06 (m, 4H) 2.40-2.47 (m, 3H) 2.91-3.16 (m, 2H) 3.16-3.34 (m, 2H) 3.35-3.69 (m, 3H) 7.63-7.70 (m, 1H) 7.72-7.86 (m, 2H) 8.20 (br. s., 1H) 8.42 (d, J=7.33 Hz, 2H) 8.85-9.00 (m, 2H) 9.03-9.38 (m, 1H) 12.63-13.81 (m, 1H). MS m/z [M+H]+ 459.2.