Acetic Acid → 2-(4-Chloro-phenyl)-5-[4-(1-cyclopropyl-azetidin-3-yloxy)-3-methoxy-phenyl]-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

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Reaction Steps

Mix molecular sieves (100 mg, type 3A), 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (1.00 g, 2.27 mmol), and [(1-ethoxycyclopropyl)oxy]trimethylsilane (688.3 μL, 3.41 mmol), and acetic acid (651.3 μL, 11.37 mmoles) in dry methanol (11 mL) and reflux the mixture for 3 h. Cool the reaction to room temperature, then add sodium cyanoborohydride (376 mg, 5.68 mmoles) and slowly warm to 40° C. for one hour. Cool the mixture and add 1 N NaOH solution, then extract the aqueous layer with CHCl3 (3×25 mL). Dry the organic layer with Na2SO4, filter, and concentrate. Purify the crude material on silica gel chromatography using a gradient of 0-10% 2 N NH3/MeOH in CHCl3. Collect the desired fractions and remove the solvent via reduced pressure. Re-dissolve the resulting material in CHCl3 and add 1 N HCl/Et2O solution (2.27 mL). Remove the solvent and dry under vacuum to give 408 mg (35%) of the title compound. ES/MS m/z (35Cl) 480.0 [M+1]+.

Provenance & Evidence