反应详情

A 5 mL conical microwave vessel was charged with 6-(2-fluoro-5-((2-methoxyethoxy)methoxy)-6-(trifluoromethyl)pyridin-3-yl)-2-methylbenzo[d]thiazole (0.0186 g, 0.045 mmol), a spin vane and 1 mL TFE. The vessel was swept with Ar, treated with 2M hydrochloric acid (0.022 ml, 0.045 mmol) and sealed. The solution was irradiated using a Biotage microwave synthesizer to 120° C. for 15 minutes. The solution was concentrated using a stream of nitrogen. The crude was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 25% B; 5.0→35 min@20 mL/min, linear gradient to 55% B; 35→45@20 mL/min, isocratic at 55% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 25% B; 60 min end. A=water; B=2% TFE in ACN. A band that eluted from 26.4 to 28.7 minutes was isolated. The solvent was concentrated under a stream of nitrogen overnight, and then lyophilized to afford 6-fluoro-5-(2-methylbenzo[d]thiazol-6-yl)-2-(trifluoromethyl)pyridin-3-ol (0.0068 g, 46% yield). 1H NMR (400 MHz, DMF) δ ppm 2.88 (s, 3H) 7.78 (dt, J=8.46, 1.78 Hz, 1H) 7.89 (d, J=7.92 Hz, 1H) 8.07 (d, J=8.51 Hz, 1H) 8.39 (t, J=1.37 Hz, 1H) 11.89 (br. s., 1H). 19F NMR (376 MHz, DMF) δ ppm −82.30 (d, J=6.50 Hz, 1 F) −64.69 (s, 3 F). HPLC-MS: 2.14 min (>99%@215 nm; >99% @254 nm; m/z=329.0, calculated for C14H8F4N2OS+H+=328.0).

1. customsealed
2. customThe solution was irradiated
3. customto 120° C.
4. customfor 15 minutes
5. concentrationThe solution was concentrated
6. customThe crude was purified
7. custom0→5 min@20 mL/min, 25% B
8. custom5.0→35 min@20 mL/min, linear gradient
9. customisocratic at 55% B, 45→55 min@20 mL/min, step
10. custom55→60 min@20 mL/min, step
11. custom60 min end
12. washA band that eluted from 26.4 to 28.7 minutes
13. customwas isolated
14. concentrationThe solvent was concentrated under a stream of nitrogen overnight