反应详情

温度

100 °C

Ethyl 1-[5-[7-[3-(1,3-dioxoisoindolin-2-yl)oxyprop-1-ynyl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (233 mg, 0.32 mmol) was suspended in EtOH (20 mL) and sodium hydroxide solution (10 mL, 1 M, aq) was added to give a light yellow solution. The solution was heated at 100° C. then cooled to rt after 48 h. The mixture was concentrated to dryness under reduced pressure and remaining water azeotroped with MeCN. The resulting yellow residue was suspended in MeOH with sonication and warming then filtered through a PTFE filter cup. A white (salt-like) solid was obtained (discarded) and a yellow filtrate. The yellow filtrate was concentrated to dryness under reduced pressure to give a yellow solid which was suspended in water, sonicated, DCM added and the mixture filtered through a PTFE filter cup leaving a pale yellow solid. This solid was dissolved in MeOH, passed through the filter cup and the solution concentrated to dryness under reduced pressure to give a pale yellow solid which was purified by chromatography, Biotage SP4, 40 g Si cartridge, 0-5% MeOH in DCM. The relevant fractions were combined to afford Compound 197 as a pale yellow solid, 9 mg. 1H NMR (MeOD): δ 8.67 (2H, s), 7.85 (1H, d, J=1.6 Hz), 7.51 (1H, d, J=1.6 Hz), 4.57 (2H, t, J=10.2 Hz), 4.57 (2H, m), 3.60 (2H, t, J=10.2 Hz), 3.36 (2H, q, J=7.2 Hz), 3.24 (2H, m), 2.22 (2H, dm, J=13.4 Hz), 1.64 (2H, J=7.5 Hz), 1.45 (2H, m), 1.24 (3H, t, J=7.2 Hz), 0.93 (3H, t, J=7.5 Hz). MS: 524.14 [M+H]+.

1. customto give a light yellow solution
2. temperaturethen cooled to rt after 48 h
3. concentrationThe mixture was concentrated to dryness under reduced pressure
4. customazeotroped with MeCN
5. customThe resulting yellow residue was suspended in MeOH with sonication
6. temperaturewarming
7. filtrationthen filtered through a PTFE
8. filtrationfilter
9. customA white (salt-like) solid was obtained (discarded)
10. concentrationThe yellow filtrate was concentrated to dryness under reduced pressure
11. customto give a yellow solid which
12. customsonicated
13. filtrationthe mixture filtered through a PTFE
14. filtrationfilter
15. customcup leaving a pale yellow solid
16. concentrationthe solution concentrated to dryness under reduced pressure
17. customto give a pale yellow solid which
18. customwas purified by chromatography, Biotage SP4, 40 g Si cartridge, 0-5% MeOH in DCM