N,N-dimethylazetidin-3-amine hydrochloride

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6 H) 2.36 (s, 3 H) 2.52-2.58 (m, 1 H) 2.61-2.68 (m, 1 H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1 H) 3.87 (d, J=5.05 Hz, 1 H) 4.07 (t, J=8.34 Hz, 1 H) 4.20 (br. s., 1 H) 4.37 (t, J=7.83 Hz, 1 H) 7.57 (dd, J=7.96, 1.39 Hz, 1 H) 7.63 (s, 1 H) 7.75 (d, J=8.08 Hz, 1 H) 8.06 (s, 1 H) 8.17 (dd, J=8.59, 2.27 Hz, 1 H) 8.34 (d, J=8.84 Hz, 1 H) 8.66 (dd, J=2.27, 0.76 Hz, 1 H); ESI-MS m/z [M+H]+ 403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6 H) 2.36 (s, 3 H) 2.52-2.58 (m, 1 H) 2.61-2.68 (m, 1 H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1 H) 3.87 (d, J=5.05 Hz, 1 H) 4.07 (t, J=8.34 Hz, 1 H) 4.20 (br. s., 1 H) 4.37 (t, J=7.83 Hz, 1 H) 7.57 (dd, J=7.96, 1.39 Hz, 1 H) 7.63 (s, 1 H) 7.75 (d, J=8.08 Hz, 1 H) 8.06 (s, 1 H) 8.17 (dd, J=8.59, 2.27 Hz, 1 H) 8.34 (d, J=8.84 Hz, 1 H) 8.66 (dd, J=2.27, 0.76 Hz, 1 H); ESI-MS m/z [M+H]+ 403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6H) 2.36 (s, 3H) 2.52-2.58 (m, 1H) 2.61-2.68 (m, 1H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1H) 3.87 (d, J=5.05 Hz, 1H) 4.07 (t, J=8.34 Hz, 1H) 4.20 (br. s., 1H) 4.37 (t, J=7.83 Hz, 1H) 7.57 (dd, J=7.96, 1.39 Hz, 1H) 7.63 (s, 1H) 7.75 (d, J=8.08 Hz, 1H) 8.06 (s, 1H) 8.17 (dd, J=8.59, 2.27 Hz, 1H) 8.34 (d, J=8.84 Hz, 1H) 8.66 (dd, J=2.27, 0.76 Hz, 1H); ESI-MS m/z [M+H]+403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6H) 2.36 (s, 3H) 2.52-2.58 (m, 1H) 2.61-2.68 (m, 1H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1H) 3.87 (d, J=5.05 Hz, 1H) 4.07 (t, J=8.34 Hz, 1H) 4.20 (br. s., 1H) 4.37 (t, J=7.83 Hz, 1H) 7.57 (dd, J=7.96, 1.39 Hz, 1H) 7.63 (s, 1H) 7.75 (d, J=8.08 Hz, 1H) 8.06 (s, 1H) 8.17 (dd, J=8.59, 2.27 Hz, 1H) 8.34 (d, J=8.84 Hz, 1H) 8.66 (dd, J=2.27, 0.76 Hz, 1H); ESI-MS m/z [M+H]+403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6 H) 2.36 (s, 3 H) 2.52-2.58 (m, 1 H) 2.61-2.68 (m, 1 H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1 H) 3.87 (d, J=5.05 Hz, 1 H) 4.07 (t, J=8.34 Hz, 1 H) 4.20 (br. s., 1 H) 4.37 (t, J=7.83 Hz, 1 H) 7.57 (dd, J=7.96, 1.39 Hz, 1 H) 7.63 (s, 1 H) 7.75 (d, J=8.08 Hz, 1 H) 8.06 (s, 1 H) 8.17 (dd, J=8.59, 2.27 Hz, 1 H) 8.34 (d, J=8.84 Hz, 1 H) 8.66 (dd, J=2.27, 0.76 Hz, 1 H); ESI-MS m/z [M+H]+ 403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried

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 (105 mg, 0.328 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (94.0 mg, 0.490 mmol), HOBT (66.4 mg, 0.492 mmol) in DMF (1.0 mL) and added N,N-diisopropylethylamine (0.285 mL, 1.639 mmol). Then added N,N-dimethylazetidin-3-amine hydrochloride (67.2 mg, 0.492 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (3.5 mL) and acidified to pH 4 with 10% citric acid to give a solid, which was collected by filtration, washed with water, methanol, and diethyl ether and dried to give the title compound as a citrate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 6H) 2.36 (s, 3H) 2.52-2.58 (m, 1H) 2.61-2.68 (m, 1H) 3.24 (ddd, J=12.25, 7.07, 5.18 Hz, 1H) 3.87 (d, J=5.05 Hz, 1H) 4.07 (t, J=8.34 Hz, 1H) 4.20 (br. s., 1H) 4.37 (t, J=7.83 Hz, 1H) 7.57 (dd, J=7.96, 1.39 Hz, 1H) 7.63 (s, 1H) 7.75 (d, J=8.08 Hz, 1H) 8.06 (s, 1H) 8.17 (dd, J=8.59, 2.27 Hz, 1H) 8.34 (d, J=8.84 Hz, 1H) 8.66 (dd, J=2.27, 0.76 Hz, 1H); ESI-MS m/z [M+H]+403.1. to give a solid, which was collected by filtration washed with water, methanol, and diethyl ether dried