(2,4-difluorophenyl)-piperazin-1-ylmethanone;hydrochloride

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title B compound, (2,4-difluorophenyl)piperazin-1-yl-methanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give (4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)(2,4-difluorophenyl)methanone: LC/MS (M+1=493.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (m, 2H), 2.72 (t, 2H, J=6.0 Hz), 3.17 (m, 2H), 3.34 (m, 2H), 3.60 (m, 2H), 4.25 (t, 2H, J=6.0 Hz), 6.59 (d, 1H, J=3.2 Hz), 6.72 (m, 1H), 7.18 (m, 3H), 7.38 (m, 1H), 7.46 (m, 1H), 7.54 (brs, 2H, NH2), 7.93 (s, 1H). Anal. calculated for (C24H22F2N8O2+0.5H2O): C, 57.48; H, 4.62; F, 7.58; N, 22.34; 0, 7.98. Found C, 57.40; H, 4.46; N, 22.29. The reaction mixture is cooled to RT the solvent is removed under reduced pressure To the residue, acetonitrile is added the solution is stirred at 60° C. for 0.5 h The solution is then cooled to RT the resulting solids are collected by filtration

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title B compound, (2,4-difluorophenyl)piperazin-1-yl-methanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give (4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)(2,4-difluorophenyl)methanone: LC/MS (M+1=493.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (m, 2H), 2.72 (t, 2H, J=6.0 Hz), 3.17 (m, 2H), 3.34 (m, 2H), 3.60 (m, 2H), 4.25 (t, 2H, J=6.0 Hz), 6.59 (d, 1H, J=3.2 Hz), 6.72 (m, 1H), 7.18 (m, 3H), 7.38 (m, 1H), 7.46 (m, 1H), 7.54 (brs, 2H, NH2), 7.93 (s, 1H). Anal. calculated for (C24H22F2N8O2+0.5H2O): C, 57.48; H, 4.62; F, 7.58; N, 22.34; 0, 7.98. Found C, 57.40; H, 4.46; N, 22.29. The reaction mixture is cooled to RT the solvent is removed under reduced pressure To the residue, acetonitrile is added the solution is stirred at 60° C. for 0.5 h The solution is then cooled to RT the resulting solids are collected by filtration

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title B compound, (2,4-difluorophenyl)piperazin-1-yl-methanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give (4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)(2,4-difluorophenyl)methanone: LC/MS (M+1=493.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (m, 2H), 2.72 (t, 2H, J=6.0 Hz), 3.17 (m, 2H), 3.34 (m, 2H), 3.60 (m, 2H), 4.25 (t, 2H, J=6.0 Hz), NH2), 7.93 (s, 1H). Anal. calculated for (C24H22F2N8O2+0.5 H2O): C, 57.48; H, 4.62; F, 7.58; N, 22.34; O, 7.98. Found C, 57.40; H, 4.46; N, 22.29. The reaction mixture is cooled to RT the solvent is removed under reduced pressure To the residue, acetonitrile is added the solution is stirred at 60° C. for 0.5 h The solution is then cooled to RT the resulting solids are collected by filtration

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title B compound, (2,4-difluorophenyl)piperazin-1-yl-methanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give (4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)(2,4-difluorophenyl)methanone: LC/MS (M+1=493.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (m, 2H), 2.72 (t, 2H, J=6.0 Hz), 3.17 (m, 2H), 3.34 (m, 2H), 3.60 (m, 2H), 4.25 (t, 2H, J=6.0 Hz), NH2), 7.93 (s, 1H). Anal. calculated for (C24H22F2N8O2+0.5 H2O): C, 57.48; H, 4.62; F, 7.58; N, 22.34; O, 7.98. Found C, 57.40; H, 4.46; N, 22.29. The reaction mixture is cooled to RT the solvent is removed under reduced pressure To the residue, acetonitrile is added the solution is stirred at 60° C. for 0.5 h The solution is then cooled to RT the resulting solids are collected by filtration

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title B compound, (2,4-difluorophenyl)piperazin-1-yl-methanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give (4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)(2,4-difluorophenyl)methanone: LC/MS (M+1=493.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (m, 2H), 2.72 (t, 2H, J=6.0 Hz), 3.17 (m, 2H), 3.34 (m, 2H), 3.60 (m, 2H), 4.25 (t, 2H, J=6.0 Hz), 6.59 (d, 1H, J=3.2 Hz), 6.72 (m, 1H), 7.18 (m, 3H), 7.38 (m, 1H), 7.46 (m, 1H), 7.54 (brs, 2H, NH2), 7.93 (s, 1H). Anal. calculated for (C24H22F2N8O2+0.5H2O): C, 57.48; H, 4.62; F, 7.58; N, 22.34; 0, 7.98. Found C, 57.40; H, 4.46; N, 22.29. The reaction mixture is cooled to RT the solvent is removed under reduced pressure To the residue, acetonitrile is added the solution is stirred at 60° C. for 0.5 h The solution is then cooled to RT the resulting solids are collected by filtration