(2S)-1-ethyl-2-methylpiperazine

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 112 using 6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.30 (m, 6 H) 2.41 (s, 3 H) 2.79 (dt, J=12.95, 6.54 Hz, 2 H) 2.94-3.10 (m, 2 H) 3.13 (d, J=11.37 Hz, 1 H) 3.23 (dd, J=13.14, 8.34 Hz, 1 H) 3.46 (br. s., 1 H) 3.61-4.25 (m, 2 H) 7.59 (d, J=7.33 Hz, 1 H) 7.91-8.00 (m, 1 H) 8.03 (s, 1 H) 8.30 (d, J=13.14 Hz, 1 H) 8.45-8.57 (m, 2 H); ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87-1.19 (m, 6 H) 2.42 (s, 3 H) 2.47 (br. s., 1 H) 2.52-2.59 (m, 1 H) 2.62-2.76 (m, 1 H) 2.77-2.98 (m, 2 H) 3.06 (d, J=10.61 Hz, 1 H) 3.35 (br. s., 1 H) 3.46-3.75 (m, 1 H) 4.05 (br. s., 1 H) 7.60 (dd, J=7.96, 1.64 Hz, 1 H) 7.66 (d, J=1.26 Hz, 1 H) 7.90 (d, J=8.34 Hz, 1 H) 8.01 (dd, J=8.72, 2.15 Hz, 1H) 8.06 (s, 1 H) 8.43 (d, J=8.59 Hz, 1 H) 8.51 (d, J=1.77 Hz, 1 H) 11.83-12.92 (m, 1 H); ESI-MS m/z [M+H]+ 431.3.

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 112 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87-1.19 (m, 6 H) 2.42 (s, 3 H) 2.47 (br. s., 1 H) 2.52-2.59 (m, 1 H) 2.62-2.76 (m, 1 H) 2.77-2.98 (m, 2 H) 3.06 (d, J=10.61 Hz, 1 H) 3.35 (br. s., 1 H) 3.46-3.75 (m, 1 H) 4.05 (br. s., 1 H) 7.60 (dd, J=7.96, 1.64 Hz, 1 H) 7.66 (d, J=1.26 Hz, 1 H) 7.90 (d, J=8.34 Hz, 1 H) 8.01 (dd, J=8.72, 2.15 Hz, 1H) 8.06 (s, 1 H) 8.43 (d, J=8.59 Hz, 1 H) 8.51 (d, J=1.77 Hz, 1 H) 11.83-12.92 (m, 1 H); ESI-MS m/z [M+H]+ 431.3.

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-cyano-3-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (t, J=7.20 Hz, 6 H) 2.33 (d, J=2.27 Hz, 3 H) 3.08-3.36 (m, 4 H) 3.42 (br. s., 2 H) 4.11-4.93 (m, 3 H) 7.64 (br. s., 1 H) 7.71-7.80 (m, 1 H) 7.87-8.79 (m, 4 H) 9.53-10.44 (m, 1 H) 12.23-14.36 (m, 1H). ESI-MS m/z [M+H]+ 449.3.

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-cyano-3-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (t, J=7.20 Hz, 6 H) 2.33 (d, J=2.27 Hz, 3 H) 3.08-3.36 (m, 4 H) 3.42 (br. s., 2 H) 4.11-4.93 (m, 3 H) 7.64 (br. s., 1 H) 7.71-7.80 (m, 1 H) 7.87-8.79 (m, 4 H) 9.53-10.44 (m, 1 H) 12.23-14.36 (m, 1H). ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.30 (m, 6H) 2.41 (s, 3H) 2.79 (dt, J=12.95, 6.54 Hz, 2H) 2.94-3.10 (m, 2H) 3.13 (d, J=11.37 Hz, 1H) 3.23 (dd, J=13.14, 8.34 Hz, 1H) 3.46 (br. s., 1H) 3.61-4.25 (m, 2H) 7.59 (d, J=7.33 Hz, 1H) 7.91-8.00 (m, 1H) 8.03 (s, 1H) 8.30 (d, J=13.14 Hz, 1H) 8.45-8.57 (m, 2H); ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.30 (m, 6H) 2.41 (s, 3H) 2.79 (dt, J=12.95, 6.54 Hz, 2H) 2.94-3.10 (m, 2H) 3.13 (d, J=11.37 Hz, 1H) 3.23 (dd, J=13.14, 8.34 Hz, 1H) 3.46 (br. s., 1H) 3.61-4.25 (m, 2H) 7.59 (d, J=7.33 Hz, 1H) 7.91-8.00 (m, 1H) 8.03 (s, 1H) 8.30 (d, J=13.14 Hz, 1H) 8.45-8.57 (m, 2H); ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87-1.19 (m, 6H) 2.42 (s, 3H) 2.47 (br. s., 1H) 2.52-2.59 (m, 1H) 2.62-2.76 (m, 1H) 2.77-2.98 (m, 2H) 3.06 (d, J=10.61 Hz, 1H) 3.35 (br. s., 1H) 3.46-3.75 (m, 1H) 4.05 (br. s., 1H) 7.60 (dd, J=7.96, 1.64 Hz, 1H) 7.66 (d, J=1.26 Hz, 1H) 7.90 (d, J=8.34 Hz, 1H) 8.01 (dd, J=8.72, 2.15 Hz, 1H) 8.06 (s, 1H) 8.43 (d, J=8.59 Hz, 1H) 8.51 (d, J=1.77 Hz, 1H) 11.83-12.92 (m, 1H); ESI-MS m/z [M+H]+ 431.3.

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 112 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87-1.19 (m, 6H) 2.42 (s, 3H) 2.47 (br. s., 1H) 2.52-2.59 (m, 1H) 2.62-2.76 (m, 1H) 2.77-2.98 (m, 2H) 3.06 (d, J=10.61 Hz, 1H) 3.35 (br. s., 1H) 3.46-3.75 (m, 1H) 4.05 (br. s., 1H) 7.60 (dd, J=7.96, 1.64 Hz, 1H) 7.66 (d, J=1.26 Hz, 1H) 7.90 (d, J=8.34 Hz, 1H) 8.01 (dd, J=8.72, 2.15 Hz, 1H) 8.06 (s, 1H) 8.43 (d, J=8.59 Hz, 1H) 8.51 (d, J=1.77 Hz, 1H) 11.83-12.92 (m, 1H); ESI-MS m/z [M+H]+ 431.3.

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-cyano-3-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (t, J=7.20 Hz, 6H) 2.33 (d, J=2.27 Hz, 3H) 3.08-3.36 (m, 4H) 3.42 (br. s., 2H) 4.11-4.93 (m, 3H) 7.64 (br. s., 1H) 7.71-7.80 (m, 1H) 7.87-8.79 (m, 4H) 9.53-10.44 (m, 1H) 12.23-14.36 (m, 1H). ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95-1.30 (m, 6 H) 2.41 (s, 3 H) 2.79 (dt, J=12.95, 6.54 Hz, 2 H) 2.94-3.10 (m, 2 H) 3.13 (d, J=11.37 Hz, 1 H) 3.23 (dd, J=13.14, 8.34 Hz, 1 H) 3.46 (br. s., 1 H) 3.61-4.25 (m, 2 H) 7.59 (d, J=7.33 Hz, 1 H) 7.91-8.00 (m, 1 H) 8.03 (s, 1 H) 8.30 (d, J=13.14 Hz, 1 H) 8.45-8.57 (m, 2 H); ESI-MS m/z [M+H]+ 449.3.

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 112 using 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid and (S)-1-ethyl-2-methylpiperazine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87-1.19 (m, 6 H) 2.42 (s, 3 H) 2.47 (br. s., 1 H) 2.52-2.59 (m, 1 H) 2.62-2.76 (m, 1 H) 2.77-2.98 (m, 2 H) 3.06 (d, J=10.61 Hz, 1 H) 3.35 (br. s., 1 H) 3.46-3.75 (m, 1 H) 4.05 (br. s., 1 H) 7.60 (dd, J=7.96, 1.64 Hz, 1 H) 7.66 (d, J=1.26 Hz, 1 H) 7.90 (d, J=8.34 Hz, 1 H) 8.01 (dd, J=8.72, 2.15 Hz, 1H) 8.06 (s, 1 H) 8.43 (d, J=8.59 Hz, 1 H) 8.51 (d, J=1.77 Hz, 1 H) 11.83-12.92 (m, 1 H); ESI-MS m/z [M+H]+ 431.3.