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

Participants

Reaction Conditions

Reaction Steps

Cool a mixture of 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt (20 g, 42.0 mmol) in methanol (600 mL) to 15° C. Add acetic acid (12.1 mL, 211.6 mmol) and sodium cyanoborohydride (7 g, 111 mmol). Add formaldehyde (10.2 mL, 136.45 mmol, as a solution in water to the thick mixture and stir for 15 h at room temperature. Cool the mixture to 5° C., add saturated aqueous NaHCO3 (320 mL), and stir the mixture for one hour at room temperature. Extract the mixture with CHCl3 (3×1 L). Combine the organic solutions and wash with brine, then dry, filter, and concentrate. Dissolve the residue in CHCl3 (240 mL) and dilute with tert-butyl methyl ether (700 mL). Collect the precipitate by filtration and rinse the solids with additional tert-butyl methyl ether. Dry the solid under vacuum for 5 h at room temperature to obtain 5.4 g (81%) of the title compound. ES/MS m/z (35Cl) 454 [M+1]+.

Provenance & Evidence