反应详情

温度

100 °C

Combined 6-(5-methoxy-4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (25.8 mg, 0.063 mmol) and lithium chloride (13.42 mg, 0.317 mmol) in DMA (0.5 mL) and then heated at 50° C. using a heating block for 2 days. Additional portion of lithium chloride (13.42 mg, 0.317 mmol) was added and the reaction mixture was stirred at 100° C. for 17 hours. The reaction mixture was cooled to 23° C., filtered through a Hydrophilic PTFE 0.45 um filter (Millipore Millex™-LCR), rinsed with DMSO (2×0.5 mL), and purified via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm) using a gradient of 10-40% ACN (with 0.035% TFA) in water (with 0.05% TFA) to give a residue. The residue was dissolved in DMSO, filtered through a Hydrophilic PTFE 0.45 um filter (Millipore Millex™-LCR), rinsed with DMSO, and purified again via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm) using an isocratic method of 17% ACN (with 0.05% TFA) in water (with 0.05% TFA) to give the title compound, as a TFA salt, (6.2 mg, 19.30% yield) as a green oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.26 (m, 2 H) 1.55-1.67 (m, 2 H) 1.77-1.84 (m, 1 H) 2.51 (br. s., 3 H) 3.17-3.24 (m, 2 H) 3.24-3.32 (m, 2 H) 3.83-3.88 (m, 2 H) 7.77-8.07 (m, 2 H) 8.07-8.22 (m, 1 H) 8.22-8.30 (m, 1 H) 8.36-8.44 (m, 1 H) 8.58-8.67 (m, 1 H) 8.67-8.81 (m, 1 H) 8.81-8.92 (m, 1 H) 13.58 (br. s., 1 H). MS m/z [M+H]+ 394.5.

1. customfor 2 days
2. temperatureThe reaction mixture was cooled to 23° C.
3. filtrationfiltered through a Hydrophilic PTFE 0.45 um
4. filtrationfilter (Millipore Millex™-LCR)
5. washrinsed with DMSO (2×0.5 mL)
6. custompurified via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm)
7. customto give a residue
8. filtrationfiltered through a Hydrophilic PTFE 0.45 um
9. filtrationfilter (Millipore Millex™-LCR)
10. washrinsed with DMSO
11. custompurified again via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm)