反应详情

温度

60 °C

1-{3-[4-(4-chlorobenzyl)-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridin-5-yl}-N-(2,4-dimethoxybenzyl)methanamine (0.257 g, 0.438 mmol) was dissolved in methylene chloride (6.0 mL) and trifluoroacetic acid (6.0 mL). Trifluoromethanesulfonic acid (0.050 mL, 0.56 mmol) was added and the mixture was heated to 60° C. for 6 days. The mixture was evaporated in a rotary evaporator, azeotroped with EtOAc (3×), and evaporated to give a crude residue. The residue was suspended in ˜1 mL of MeOH and diluted with ˜20 mL of Et2O. The resulting powder was collected by filtration and dried under high vacuum to afford a pale pink solid product. The solid was taken up in EtOAc/water (20 mL/10 mL) and adjusted to ˜pH 8 with NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined EtOAc solutions were washed with water, brine, dried over Na2SO4, and filtered. The filtrate was concentrated to ˜5 mL volume and the precipitated solid was collected by filtration to give a pure crop of product (0.0069 g). The filtrate was evaporated then dried under high vacuum to afford a second crop of solid product (0.171 g, yield for 2 crops 89.9%). LCMS: (FA) ES+ 436, 438; ES− 434, 436. 1H NMR (400 MHz, d4-methanol) δ: 8.33-8.35 (d, J=7.29 Hz, 1H), 8.24 (s, 1H), 8.09 (s, 1H), 7.31-7.33 (d, J=8.78 Hz, 2H), 7.20-7.22 (d, J=8.53 Hz, 2H), 6.98-7.00 (m, 1H), 4.59 (s, 2H), 4.06 (s, 2H), 2.67 (s, 3H).

1. customThe mixture was evaporated in a rotary evaporator
2. customazeotroped with EtOAc (3×)
3. customevaporated
4. customto give a crude residue
5. filtrationThe resulting powder was collected by filtration
6. customdried under high vacuum
7. customto afford a pale pink solid product
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
10. washThe combined EtOAc solutions were washed with water, brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationThe filtrate was concentrated to ˜5 mL volume
14. filtrationthe precipitated solid was collected by filtration