1-(4-fluorophenyl)-2-piperazin-1-ylethanone;dihydrochloride

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-tert-butyl-1-methyl-1H-pyrazole-5-carboxylic acid (27.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (35.5 mg) as a yellow solid. Exact mass calculated for C21H27FN4O2: 386.2. Found: LCMS m/z=387.5 (M+H+). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-methyl-1-phenyl-1H-pyrazole-5-carboxylic acid (30.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (31.9 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.60-2.67 (m, 2H), 2.69 (bs., 2H), 3.81 (s, 2H), 3.89 (bs, 2H), 4.16 (bs, 2H), 6.62 (s, 1H), 7.13 (t, J=8.46 Hz, 2H), 7.38-7.54 (m, 5H), 7.99-8.09 (m, 2H). Exact mass calculated for C23H23FN4O2: 406.2. Found: LCMS m/z=407.5 (M+H+). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 4-chloro-1H-pyrazole-3-carboxylic acid (22.0 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (22.9 mg) as a white solid. Exact mass calculated for C16H16ClFN4O2: 350.1. Found: LCMS m/z (%)=351.3 (M+H+35Cl, 100%), 353.3 (M+H+37Cl, 32%). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-isopropyl-1H-pyrazole-5-carboxylic acid (23.1 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (27.1 mg) as a white solid. Exact mass calculated for C19H23FN4O2: 358.2. Found: LCMS m/z=359.3 (M+H+). The title compound was prepared in a similar manner

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

Procedure: To a solution of 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg, 0.100 mmol, from Step B of Example 1.1), 3-methyl-1H-pyrazole-5-carboxylic acid (18.9 mg, 0.150 mmol), and triethylamine (0.139 mL, 1.00 mmol) in DMF (0.5 mL) was added 1-propylphosphonic acid anhydride solution (50 wt. % in ethyl acetate, 122 μL, 0.200 mmol). The mixture was stirred for 2 h, quenched with water and purified by preparative HPLC/MS. The resultant lyophilate was dissolved in DCM, treated with MP-carbonate resin (˜100 mg). The mixture was stirred for 30 min and filtered to remove the resin. The solvent was removed under reduce pressure to afford the title compound (26.0 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.66 (bs, 4H), 3.82 (s, 2H), 3.88 (bs, 2H), 4.02 (bs, 2H), 6.38 (s, 1H), 7.14 (t, J=8.59 Hz, 2H), 7.99-8.09 (m, 2H). Exact mass calculated for Cl17H19FN4O2: 330.2. Found: LCMS m/z=331.3 (M+H+). quenched with water purified by preparative HPLC/MS The resultant lyophilate was dissolved in DCM treated with MP-carbonate resin (˜100 mg) The mixture was stirred for 30 min filtered to remove the resin The solvent was removed

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-tert-butyl-1-methyl-1H-pyrazole-5-carboxylic acid (27.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (35.5 mg) as a yellow solid. Exact mass calculated for C21H27FN4O2: 386.2. Found: LCMS m/z=387.5 (M+H+). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-methyl-1-phenyl-1H-pyrazole-5-carboxylic acid (30.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (31.9 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.60-2.67 (m, 2H), 2.69 (bs., 2H), 3.81 (s, 2H), 3.89 (bs, 2H), 4.16 (bs, 2H), 6.62 (s, 1H), 7.13 (t, J=8.46 Hz, 2H), 7.38-7.54 (m, 5H), 7.99-8.09 (m, 2H). Exact mass calculated for C23H23FN4O2: 406.2. Found: LCMS m/z=407.5 (M+H+). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 4-chloro-1H-pyrazole-3-carboxylic acid (22.0 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (22.9 mg) as a white solid. Exact mass calculated for C16H16ClFN4O2: 350.1. Found: LCMS m/z (%)=351.3 (M+H+35Cl, 100%), 353.3 (M+H+37Cl, 32%). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-isopropyl-1H-pyrazole-5-carboxylic acid (23.1 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (27.1 mg) as a white solid. Exact mass calculated for C19H23FN4O2: 358.2. Found: LCMS m/z=359.3 (M+H+). The title compound was prepared in a similar manner

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

Procedure: To a solution of 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg, 0.100 mmol, from Step B of Example 1.1), 3-methyl-1H-pyrazole-5-carboxylic acid (18.9 mg, 0.150 mmol), and triethylamine (0.139 mL, 1.00 mmol) in DMF (0.5 mL) was added 1-propylphosphonic acid anhydride solution (50 wt. % in ethyl acetate, 122 μL, 0.200 mmol). The mixture was stirred for 2 h, quenched with water and purified by preparative HPLC/MS. The resultant lyophilate was dissolved in DCM, treated with MP-carbonate resin (˜100 mg). The mixture was stirred for 30 min and filtered to remove the resin. The solvent was removed under reduce pressure to afford the title compound (26.0 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.66 (bs, 4H), 3.82 (s, 2H), 3.88 (bs, 2H), 4.02 (bs, 2H), 6.38 (s, 1H), 7.14 (t, J=8.59 Hz, 2H), 7.99-8.09 (m, 2H). Exact mass calculated for Cl17H19FN4O2: 330.2. Found: LCMS m/z=331.3 (M+H+). quenched with water purified by preparative HPLC/MS The resultant lyophilate was dissolved in DCM treated with MP-carbonate resin (˜100 mg) The mixture was stirred for 30 min filtered to remove the resin The solvent was removed

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-tert-butyl-1-methyl-1H-pyrazole-5-carboxylic acid (27.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (35.5 mg) as a yellow solid. Exact mass calculated for C21H27FN4O2: 386.2. Found: LCMS m/z=387.5 (M+H+). The title compound was prepared in a similar manner

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

Procedure: The title compound was prepared in a similar manner as described in Example 1.2, using 3-methyl-1-phenyl-1H-pyrazole-5-carboxylic acid (30.3 mg), and 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg) as starting materials, to afford the title compound (31.9 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.35 (s, 3H), 2.60-2.67 (m, 2H), 2.69 (bs., 2H), 3.81 (s, 2H), 3.89 (bs, 2H), 4.16 (bs, 2H), 6.62 (s, 1H), 7.13 (t, J=8.46 Hz, 2H), 7.38-7.54 (m, 5H), 7.99-8.09 (m, 2H). Exact mass calculated for C23H23FN4O2: 406.2. Found: LCMS m/z=407.5 (M+H+). The title compound was prepared in a similar manner