反应详情

Mix molecular sieves (60 mg, type 3A), 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (1.00 g, 2.26 mmoles), [(1-ethoxycyclopropyl)oxy]trimethylsilane (685.2 μL, 3.39 mmoles), and acetic acid (648 μL, 11.31 mmoles) in dry methanol (11.4 mL). Reflux the mixture for 3 h. Cool the mixture to room temperature, add sodium cyanoborohydride (300 mg, 4.53 mmol) and slowly warm to 40° C. for 1 h. Cool the mixture and add 1 N NaOH solution. Extract the aqueous layer with CHCl3 (3×25 mL). Purify on HPLC, 4.6×150 mm Kromasil® silica, Eluent: 40% THF/heptane 0.1% N,N′-dimethylethylamine, 1 mL/min. Re-dissolve the material in CHCl3 and add 1 N HCl/Et2O solution (750 μL). Concentrate the solvent in vacuo to give 375 mg (34%) of the title compound. ES/MS m/z (35Cl) 482.2 [M+1]+.

1. temperatureReflux the mixture for 3 h
2. temperatureslowly warm to 40° C. for 1 h
3. temperatureCool the mixture
4. extractionExtract the aqueous layer with CHCl3 (3×25 mL)
5. customPurify on HPLC, 4.6×150 mm Kromasil® silica, Eluent
6. additionadd 1 N HCl/Et2O solution (750 μL)
7. concentrationConcentrate the solvent in vacuo