4-methyl-4,7-diazaspiro[2.5]octane;dihydrochloride

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26-0.83 (m, 4 H) 2.41 (d, J=3.79 Hz, 6 H) 2.89 (br. s., 2 H) 3.40-3.91 (m, 4 H) 7.73 (d, J=7.07 Hz, 1H) 7.98 (d, J=11.87 Hz, 2 H) 8.20 (s, 1 H) 8.35-8.63 (m, 2 H); ESI-MS m/z [M+H]+ 447.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.32 (br. s., 1 H) 0.50-0.78 (m, 3 H) 2.39 (s, 3 H) 2.42 (s, 3 H) 2.86 (br. s., 2 H) 3.31 (br. s., 1 H) 3.41-3.62 (m, 2 H) 3.73 (br. s., 1 H) 7.63-7.68 (m, 1 H) 7.72 (s, 1 H) 7.77 (d, J=7.83 Hz, 1 H) 8.04 (br. s., 1 H) 8.14 (s, 1 H) 8.38 (d, J=8.08 Hz, 1 H) 8.50 (br. s., 1 H) 12.85 (br. s., 1 H); ESI-MS m/z [M+H]+ 429.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26-0.83 (m, 4H) 2.41 (d, J=3.79 Hz, 6H) 2.89 (br. s., 2H) 3.40-3.91 (m, 4H) 7.73 (d, J=7.07 Hz, 1H) 7.98 (d, J=11.87 Hz, 2H) 8.20 (s, 1H) 8.35-8.63 (m, 2H); ESI-MS m/z [M+H]+ 447.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26-0.83 (m, 4H) 2.41 (d, J=3.79 Hz, 6H) 2.89 (br. s., 2H) 3.40-3.91 (m, 4H) 7.73 (d, J=7.07 Hz, 1H) 7.98 (d, J=11.87 Hz, 2H) 8.20 (s, 1H) 8.35-8.63 (m, 2H); ESI-MS m/z [M+H]+ 447.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.32 (br. s., 1H) 0.50-0.78 (m, 3H) 2.39 (s, 3H) 2.42 (s, 3H) 2.86 (br. s., 2H) 3.31 (br. s., 1H) 3.41-3.62 (m, 2H) 3.73 (br. s., 1H) 7.63-7.68 (m, 1H) 7.72 (s, 1H) 7.77 (d, J=7.83 Hz, 1H) 8.04 (br. s., 1H) 8.14 (s, 1H) 8.38 (d, J=8.08 Hz, 1H) 8.50 (br. s., 1H) 12.85 (br. s., 1H); ESI-MS m/z [M+H]+ 429.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26-0.83 (m, 4 H) 2.41 (d, J=3.79 Hz, 6 H) 2.89 (br. s., 2 H) 3.40-3.91 (m, 4 H) 7.73 (d, J=7.07 Hz, 1H) 7.98 (d, J=11.87 Hz, 2 H) 8.20 (s, 1 H) 8.35-8.63 (m, 2 H); ESI-MS m/z [M+H]+ 447.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.32 (br. s., 1 H) 0.50-0.78 (m, 3 H) 2.39 (s, 3 H) 2.42 (s, 3 H) 2.86 (br. s., 2 H) 3.31 (br. s., 1 H) 3.41-3.62 (m, 2 H) 3.73 (br. s., 1 H) 7.63-7.68 (m, 1 H) 7.72 (s, 1 H) 7.77 (d, J=7.83 Hz, 1 H) 8.04 (br. s., 1 H) 8.14 (s, 1 H) 8.38 (d, J=8.08 Hz, 1 H) 8.50 (br. s., 1 H) 12.85 (br. s., 1 H); ESI-MS m/z [M+H]+ 429.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26-0.83 (m, 4H) 2.41 (d, J=3.79 Hz, 6H) 2.89 (br. s., 2H) 3.40-3.91 (m, 4H) 7.73 (d, J=7.07 Hz, 1H) 7.98 (d, J=11.87 Hz, 2H) 8.20 (s, 1H) 8.35-8.63 (m, 2H); ESI-MS m/z [M+H]+ 447.3.

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 4-methyl-4,7-diazaspiro[2.5]octane dihydrochloride. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.32 (br. s., 1H) 0.50-0.78 (m, 3H) 2.39 (s, 3H) 2.42 (s, 3H) 2.86 (br. s., 2H) 3.31 (br. s., 1H) 3.41-3.62 (m, 2H) 3.73 (br. s., 1H) 7.63-7.68 (m, 1H) 7.72 (s, 1H) 7.77 (d, J=7.83 Hz, 1H) 8.04 (br. s., 1H) 8.14 (s, 1H) 8.38 (d, J=8.08 Hz, 1H) 8.50 (br. s., 1H) 12.85 (br. s., 1H); ESI-MS m/z [M+H]+ 429.3.