反应详情

温度

50 °C

Combined 6-(4-(4-cyano-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (27.3 mg, 0.063 mmol) and lithium chloride (13.41 mg, 0.316 mmol) in DMA (0.5 mL) then heated at 50° C. using a heating block for 24 hours. Additional portion of lithium chloride (8.05 mg, 0.190 mmol) was added and the reaction mixture was stirred at 50° C. for an additional 14 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 30-60% ACN (with 0.035% TFA) in water (with 0.05% TFA). The product containing fractions were combined and concentrated via rotary evaporation to furnish an off-white solid which was collected by filtration, rinsed with water (5×2 mL), and dried in vacuo to give the title compound (8.2 mg, 31.0% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15-1.28 (m, 2H) 1.58-1.67 (m, 2H) 1.75-1.86 (m, 1H) 2.43 (s, 3H) 3.20 (t, J=6.32 Hz, 2H) 3.27 (td, J=11.75, 2.02 Hz, 2H) 3.81-3.90 (m, 2H) 7.60-7.69 (m, 1H) 7.73 (s, 1H) 7.78 (br. s., 1H) 8.05-8.25 (m, 1H) 8.35-8.45 (m, 1H) 8.69-8.80 (m, 1H) 8.89-8.95 (m, 1H) 13.21 (br. s., 1H). MS m/z [M+H]+ 418.5.

1. customfor 24 hours
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. additionThe product containing fractions
8. concentrationconcentrated via rotary evaporation
9. customto furnish an off-white solid which
10. filtrationwas collected by filtration
11. washrinsed with water (5×2 mL)
12. customdried in vacuo