反应详情

温度

60 °C

Ethyl 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (101 mg, 0.20 mmol) was suspended in ethanol (2 mL) and sodium hydroxide solution (2 mL, 1 M, aq) was added to give a pale yellow solution and the mixture heated to 60° C. for 1 h 40 minutes then left to cool to rt overnight. The mixture was acidified to pH 3 with HCl solution (1 M, aq) and diluted with water. DCM was added but the material did not dissolve so the mixture was concentrated under reduced pressure to remove the DCM then filtered through a PTFE filter (the filter was treated with ˜2 mL DCM to make it more permeable to aqueous suspensions) and rinsed with water (2 mL). A white solid was obtained which was dried in a vacuum oven at 40° C. to give Compound 198, 75 mg (79%). 1H NMR (DMSO): δ 1.11 (3H, t, J=7.1 Hz), 1.21 (3H, s), 1.40 (2H, ddd, J=13.8, 9.9 and 3.8 Hz), 2.02 (2H, dt, J=13.8 and 3.8 Hz), 3.20 (2H, dt, J=12.8 and 7.1 Hz), 3.33 (2H, m), 3.83 (3H, s), 4.28 (2H, dt, J=13.8 and 4.5 Hz), 6.71 (1H, br t, J=5.7 Hz), 7.56 (1H, s), 7.65 (1H, s), 8.53 (2H, s), 10.56 (1H, br s), 12.44 (1H, br s). MS: 471.13 [M+H]+.

1. customto give a pale yellow solution
2. waitthen left
3. temperatureto cool to rt overnight
4. dissolutionthe material did not dissolve so the mixture
5. concentrationwas concentrated under reduced pressure
6. customto remove the DCM
7. filtrationthen filtered through a PTFE
8. filtrationfilter (the filter
9. additionwas treated with ˜2 mL DCM
10. washrinsed with water (2 mL)
11. customA white solid was obtained which
12. customwas dried in a vacuum oven at 40° C.