N-methyl-3-piperidin-1-ylpropan-1-amine

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

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1 H) 1.66 (d, J=13.89 Hz, 3 H) 1.82 (br. s., 2 H) 2.01 (br. s., 2 H) 2.83-3.13 (m, 7 H) 3.32-3.58 (m, 4 H) 7.79 (d, J=8.34 Hz, 2 H) 8.13 (br. s., 3 H) 8.58 (br. s., 3 H) 9.05-9.50 (m, 1 H) 12.43-14.49 (m, 1 H). ESI-MS m/z [M+H]+ 445.2.

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1 H) 1.66 (d, J=13.89 Hz, 3 H) 1.82 (br. s., 2 H) 2.01 (br. s., 2 H) 2.83-3.13 (m, 7 H) 3.32-3.58 (m, 4 H) 7.79 (d, J=8.34 Hz, 2 H) 8.13 (br. s., 3 H) 8.58 (br. s., 3 H) 9.05-9.50 (m, 1 H) 12.43-14.49 (m, 1 H). ESI-MS m/z [M+H]+ 445.2.

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

Procedure: Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (70 mg, 0.219 mmol), HOBT hydrate (50.2 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (62.8 mg, 0.328 mmol) in DMF (1 mL), and added triethylamine (0.092 mL, 0.656 mmol), then stirred at ambient temperature for 5 minutes and N-methyl-3-(piperidin-1-yl)propan-1-amine (0.085 mL, 0.437 mmol) was added. The reaction was stirred at 50° C. for 3 hours. The crude reaction was then cooled to ambient temperature and diluted with DMSO (1 mL) and purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid) to give the title compound (61.5 mg, 0.134 mmol, 61.4%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30-1.49 (m, 1 H) 1.68 (br. s., 3 H) 1.82 (br. s., 2 H) 1.93-2.07 (m, 2 H) 2.43 (s, 3 H) 2.88-3.15 (m, 7 H) 3.31-3.43 (m, 1 H) 3.45-3.58 (m, 3 H) 7.65-7.87 (m, 3 H) 8.04-8.67 (m, 4 H) 9.35 (br. s., 1 H). ESI-MS m/z [M+H]+ 459.3. The reaction was stirred at 50° C. for 3 hours The crude reaction was then cooled to ambient temperature purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid)

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1H) 1.66 (d, J=13.89 Hz, 3H) 1.82 (br. s., 2H) 2.01 (br. s., 2H) 2.83-3.13 (m, 7H) 3.32-3.58 (m, 4H) 7.79 (d, J=8.34 Hz, 2H) 8.13 (br. s., 3H) 8.58 (br. s., 3H) 9.05-9.50 (m, 1H) 12.43-14.49 (m, 1H). ESI-MS m/z [M+H]+ 445.2.

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1H) 1.66 (d, J=13.89 Hz, 3H) 1.82 (br. s., 2H) 2.01 (br. s., 2H) 2.83-3.13 (m, 7H) 3.32-3.58 (m, 4H) 7.79 (d, J=8.34 Hz, 2H) 8.13 (br. s., 3H) 8.58 (br. s., 3H) 9.05-9.50 (m, 1H) 12.43-14.49 (m, 1H). ESI-MS m/z [M+H]+ 445.2.

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

Procedure: Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (70 mg, 0.219 mmol), HOBT hydrate (50.2 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (62.8 mg, 0.328 mmol) in DMF (1 mL), and added triethylamine (0.092 mL, 0.656 mmol), then stirred at ambient temperature for 5 minutes and N-methyl-3-(piperidin-1-yl)propan-1-amine (0.085 mL, 0.437 mmol) was added. The reaction was stirred at 50° C. for 3 hours. The crude reaction was then cooled to ambient temperature and diluted with DMSO (1 mL) and purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid) to give the title compound (61.5 mg, 0.134 mmol, 61.4%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30-1.49 (m, 1H) 1.68 (br. s., 3H) 1.82 (br. s., 2H) 1.93-2.07 (m, 2H) 2.43 (s, 3H) 2.88-3.15 (m, 7H) 3.31-3.43 (m, 1H) 3.45-3.58 (m, 3H) 7.65-7.87 (m, 3H) 8.04-8.67 (m, 4H) 9.35 (br. s., 1H). ESI-MS m/z [M+H]+ 459.3. The reaction was stirred at 50° C. for 3 hours The crude reaction was then cooled to ambient temperature purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid)

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

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

Procedure: Similar procedure as described in example 384 was used, starting from 1-Isopropoxy-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinoline-6-carboxylic acid and Methyl-(3-piperidin-1-yl-propyl)-amine to give 1-Isopropoxy-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinoline-6-carboxylic acid methyl-(3-piperidin-1-yl-propyl)-amide. LC-MS: m/e 465 (MH+).

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1 H) 1.66 (d, J=13.89 Hz, 3 H) 1.82 (br. s., 2 H) 2.01 (br. s., 2 H) 2.83-3.13 (m, 7 H) 3.32-3.58 (m, 4 H) 7.79 (d, J=8.34 Hz, 2 H) 8.13 (br. s., 3 H) 8.58 (br. s., 3 H) 9.05-9.50 (m, 1 H) 12.43-14.49 (m, 1 H). ESI-MS m/z [M+H]+ 445.2.

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

Procedure: Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (70 mg, 0.219 mmol), HOBT hydrate (50.2 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (62.8 mg, 0.328 mmol) in DMF (1 mL), and added triethylamine (0.092 mL, 0.656 mmol), then stirred at ambient temperature for 5 minutes and N-methyl-3-(piperidin-1-yl)propan-1-amine (0.085 mL, 0.437 mmol) was added. The reaction was stirred at 50° C. for 3 hours. The crude reaction was then cooled to ambient temperature and diluted with DMSO (1 mL) and purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid) to give the title compound (61.5 mg, 0.134 mmol, 61.4%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30-1.49 (m, 1 H) 1.68 (br. s., 3 H) 1.82 (br. s., 2 H) 1.93-2.07 (m, 2 H) 2.43 (s, 3 H) 2.88-3.15 (m, 7 H) 3.31-3.43 (m, 1 H) 3.45-3.58 (m, 3 H) 7.65-7.87 (m, 3 H) 8.04-8.67 (m, 4 H) 9.35 (br. s., 1 H). ESI-MS m/z [M+H]+ 459.3. The reaction was stirred at 50° C. for 3 hours The crude reaction was then cooled to ambient temperature purified via preparative HPLC (25-45% acetonitrile in water, with trifluoroacetic acid)

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

Procedure: The title compound was prepared in a manner similar to Example 303 using 6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and N-methyl-3-(piperidin-1-yl)propyl amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=9.60 Hz, 1H) 1.66 (d, J=13.89 Hz, 3H) 1.82 (br. s., 2H) 2.01 (br. s., 2H) 2.83-3.13 (m, 7H) 3.32-3.58 (m, 4H) 7.79 (d, J=8.34 Hz, 2H) 8.13 (br. s., 3H) 8.58 (br. s., 3H) 9.05-9.50 (m, 1H) 12.43-14.49 (m, 1H). ESI-MS m/z [M+H]+ 445.2.