N-(4-磺酰基苯基)甲胺环丙羧酸

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(4-mercaptophenyl)cyclopropane carboxamide (16.1 mmol) in THF (25 mL) at 0° C. was added sodium hydride (16.1 mmol) portionwise. Once the addition was complete the resulting solution was stirred at room temperature for 30 min. After this time, the reaction mixture was cooled to 0° C. and a solution of 2,6-dichloropyrazine (13.4 mmol) was added and the resulting mixture stirred at room temperature for 16 h. Water (30 mL) and ethyl acetate (30 mL) were added and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×30 mL), the combined organic layers dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc) to give the title compound (2.95 g, 72%) as a cream coloured solid; 1H NMR (400 MHz, DMSO-d6) δ 0.91 (2H, m), 1.13 (2H, m), 1.54 (1H, m), 7.53 (1H, br s), 7.57 (2H, m), 7.65 (2H, m), 7.96 (1H, s), 8.22 (1H, s); MS (ES+): m/e=306.14 (100%). Once the addition After this time, the reaction mixture was cooled to 0° C. the resulting mixture stirred at room temperature for 16 h the layers separated The aqueous layer was extracted further with ethyl acetate (2×30 mL) the combined organic layers dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(4-mercaptophenyl)cyclopropane carboxamide (16.1 mmol) in THF (25 mL) at 0° C. was added sodium hydride (16.1 mmol) portionwise. Once the addition was complete the resulting solution was stirred at room temperature for 30 min. After this time, the reaction mixture was cooled to 0° C. and a solution of 2,6-dichloropyrazine (13.4 mmol) was added and the resulting mixture stirred at room temperature for 16 h. Water (30 mL) and ethyl acetate (30 mL) were added and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×30 mL), the combined organic layers dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc) to give the title compound (2.95 g, 72%) as a cream coloured solid; 1H NMR (400 MHz, DMSO-d6) δ 0.91 (2H, m), 1.13 (2H, m), 1.54 (1H, m), 7.53 (1H, br s), 7.57 (2H, m), 7.65 (2H, m), 7.96 (1H, s), 8.22 (1H, s); MS (ES+): m/e=306.14 (100%). Once the addition After this time, the reaction mixture was cooled to 0° C. the resulting mixture stirred at room temperature for 16 h the layers separated The aqueous layer was extracted further with ethyl acetate (2×30 mL) the combined organic layers dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc)

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 7-chloro-2-ethyl-N-(5-methyl-1H-pyrazol-3-yl)imidazo[1,2-c]pyrimidin-5-amine 0.22 mmol, 0.06 g) was dissolved in DMF (1 mL). N-(4-mercaptophenyl)cyclopropanecarboxamide (0.24 mmol, 0.046 g) and K2CO3 (0.24 mmol, 0.033 g) was added. The reaction mixture was heated to 160° C. using a microwave reactor for 20 minutes. The mixture was then concentrated and purified by LC-MS to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.83-0.84 (m, 4H) 1.25 (t, J=7.45 Hz, 3H) 1.79-1.86 (m, 1H) 2.12 (s, 3H) 2.73 (q, J=7.24 Hz, 2H) 5.80 (s, 1H) 6.65 (s, 1H) 7.58 (d, J=8.59 Hz, 2H) 7.81 (d, J=8.59 Hz, 2H) 8.31 (s, 1H) 10.55 (s, 1H) 10.97 (s, 1H) 12.30 (s, 1H); ESI-MS: m/z calc'd for C22H23N7OS 433.53; found 434.4 (M+H)+. for 20 minutes The mixture was then concentrated purified by LC-MS

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 7-chloro-2-ethyl-N-(5-methyl-1H-pyrazol-3-yl)imidazo[1,2-c]pyrimidin-5-amine 0.22 mmol, 0.06 g) was dissolved in DMF (1 mL). N-(4-mercaptophenyl)cyclopropanecarboxamide (0.24 mmol, 0.046 g) and K2CO3 (0.24 mmol, 0.033 g) was added. The reaction mixture was heated to 160° C. using a microwave reactor for 20 minutes. The mixture was then concentrated and purified by LC-MS to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.83-0.84 (m, 4H) 1.25 (t, J=7.45 Hz, 3H) 1.79-1.86 (m, 1H) 2.12 (s, 3H) 2.73 (q, J=7.24 Hz, 2H) 5.80 (s, 1H) 6.65 (s, 1H) 7.58 (d, J=8.59 Hz, 2H) 7.81 (d, J=8.59 Hz, 2H) 8.31 (s, 1H) 10.55 (s, 1H) 10.97 (s, 1H) 12.30 (s, 1H); ESI-MS: m/z calc'd for C22H23N7OS 433.53; found 434.4 (M+H)+. for 20 minutes The mixture was then concentrated purified by LC-MS

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 7-chloro-2-ethyl-N-(5-methyl-1H-pyrazol-3-yl)imidazo[1,2-c]pyrimidin-5-amine 0.22 mmol, 0.06 g) was dissolved in DMF (1 mL). N-(4-mercaptophenyl)cyclopropanecarboxamide (0.24 mmol, 0.046 g) and K2CO3 (0.24 mmol, 0.033 g) was added. The reaction mixture was heated to 160° C. using a microwave reactor for 20 minutes. The mixture was then concentrated and purified by LC-MS to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.83-0.84 (m, 4H) 1.25 (t, J=7.45 Hz, 3H) 1.79-1.86 (m, 1H) 2.12 (s, 3H) 2.73 (q, J=7.24 Hz, 2H) 5.80 (s, 1H) 6.65 (s, 1H) 7.58 (d, J=8.59 Hz, 2H) 7.81 (d, J=8.59 Hz, 2H) 8.31 (s, 1H) 10.55 (s, 1H) 10.97 (s, 1H) 12.30 (s, 1H); ESI-MS: m/z calc'd for C22H23N7OS 433.53; found 434.4 (M+H)+. for 20 minutes The mixture was then concentrated purified by LC-MS

反应条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (7-Chloro-imidazo[1,2-a]pyrimidin-5-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (73 mg, 0.29 mmol), N-(4-mercaptophenyl)cyclopropanecarboxamide (170 mg, 0.88 mmol), potassium carbonate (81 mg, 0.58 mmol) in DMF (1 ml) was heated with microwave at 190° C. for 30 minutes. The reaction mixture was then purified by HPLC to give the title compound Example 10 as an off-white solid (110 mg). 1H NMR (400 MHz, DMSO) δ 10.54 (s, 1H) 8.26 (d, J=2.8 Hz, 1H) 7.97 (d, J=2.4 Hz, 1H) 7.79 (d, J=8.8 Hz, 2H) 7.57 (d, J=8.8 Hz, 2H) 6.89 (s, 1H) 5.82 (s, 1H) 2.20 (s, 3H) 1.81-1.85 (m, 1H) 0.84-0.86 (m, 4H). [M+H] calc'd for C20H19N7OS, 406; found, 406. The reaction mixture was then purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (21 mg, 0.072 mmol), N-(4-mercaptophenyl)cyclopropanecarboxamide (28 mg, 0.145 mmol) and potassium carbonate (20 mg) were mixed in DMF (1 ml). This mixture was reacted in a microwave reactor at 170° C. for 15 minutes. DMF was removed in vacuo and the residue was purified by HPLC to afford the title compound Example 8 as an off-white solid. (11.9 mg). 1H NMR (400 MHz, DMSO) δ 10.39 (s, 1H) 7.99 (d, J=0.8 Hz, 1H) 7.96 (s, 1H) 7.70 (s, 1H) 7.69 (d, J=8.4 Hz, 2H) 7.49 (d, J=8.4 Hz, 2H) 6.03 (s, 1H) 2.14 (s, 3H) 1.75-1.82 (m, 1H) 0.77-0.81 (m, 2H). [M+H] calc'd for C20H19N7OS, 406; found, 406. This mixture was reacted in a microwave reactor at 170° C. for 15 minutes DMF was removed in vacuo the residue was purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (21 mg, 0.072 mmol), N-(4-mercaptophenyl)cyclopropanecarboxamide (28 mg, 0.145 mmol) and potassium carbonate (20 mg) were mixed in DMF (1 ml). This mixture was reacted in a microwave reactor at 170° C. for 15 minutes. DMF was removed in vacuo and the residue was purified by HPLC to afford the title compound Example 8 as an off-white solid. (11.9 mg). 1H NMR (400 MHz, DMSO) δ 10.39 (s, 1H) 7.99 (d, J=0.8 Hz, 1H) 7.96 (s, 1H) 7.70 (s, 1H) 7.69 (d, J=8.4 Hz, 2H) 7.49 (d, J=8.4 Hz, 2H) 6.03 (s, 1H) 2.14 (s, 3H) 1.75-1.82 (m, 1H) 0.77-0.81 (m, 2H). [M+H] calc'd for C20H19N7OS, 406; found, 406. This mixture was reacted in a microwave reactor at 170° C. for 15 minutes DMF was removed in vacuo the residue was purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (21 mg, 0.072 mmol), N-(4-mercaptophenyl)cyclopropanecarboxamide (28 mg, 0.145 mmol) and potassium carbonate (20 mg) were mixed in DMF (1 ml). This mixture was reacted in a microwave reactor at 170° C. for 15 minutes. DMF was removed in vacuo and the residue was purified by HPLC to afford the title compound Example 8 as an off-white solid. (11.9 mg). 1H NMR (400 MHz, DMSO) δ 10.39 (s, 1H) 7.99 (d, J=0.8 Hz, 1H) 7.96 (s, 1H) 7.70 (s, 1H) 7.69 (d, J=8.4 Hz, 2H) 7.49 (d, J=8.4 Hz, 2H) 6.03 (s, 1H) 2.14 (s, 3H) 1.75-1.82 (m, 1H) 0.77-0.81 (m, 2H). [M+H] calc'd for C20H19N7OS, 406; found, 406. This mixture was reacted in a microwave reactor at 170° C. for 15 minutes DMF was removed in vacuo the residue was purified by HPLC

反应条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (7-Chloro-imidazo[1,2-a]pyrimidin-5-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (73 mg, 0.29 mmol), N-(4-mercaptophenyl)cyclopropane carboxamide (170 mg, 0.88 mmol), potassium carbonate (81 mg, 0.58 mmol) in DMF (1 ml) was heated with microwave at 190° C. for 30 minutes. The reaction mixture was then purified by HPLC to give the title compound Example 10 as an off-white solid (110 mg). 1H NMR (400 MHz, DMSO) δ 10.54 (s, 1H) 8.26 (d, J=2.8 Hz, 1H) 7.97 (d, J=2.4 Hz, 1H) 7.79 (d, J=8.8 Hz, 2H) 7.57 (d, J=8.8 Hz, 2H) 6.89 (s, 1H) 5.82 (s, 1H) 2.20 (s, 3H) 1.81-1.85 (m, 1H) 0.84-0.86 (m, 4H). [M+H] calc'd for C20H19N7OS, 406; found, 406. The reaction mixture was then purified by HPLC