A synthetic route for obtaining 1-butoxy-1,3,3-triethoxy[1,3-2H2]propane a stable diacetal of the malondialdehyde, is described. The synthesis involves the condensation of deuterated butylvinyl ether with deuterated triethyl orthoformate in the presence of montmorillonite clay K-10. The deuteration of butyl vinyl ether was accomplished via the intermediary formation of a stannane derivative which was quantitatively metallated by n-butyllithium and then treated with 2H2O. From the diacetal the 1,3-dideuterated malondialdehyde was obtained by a short treatment with acid ion exchange resin.
A robust direct enol ether metalation–Negishi coupling using heteroaryl halides catalyzed by the palladium-Cy-DPEPhos system is reported. This method, which was demonstrated with a broad substrate scope, is a highly complementary method to the existing Heck coupling of synthesizing challenging α-heteroaryl-α-alkoxy alkenes.
Disclosed are compounds of the formula (I), or a tautomeric form thereof, or a pharmaceutically acceptable salt or N-oxide thereof: (I) wherein R1, R2, R3, R4, R5, n, m, and x are as defined herein. Compounds of the invention may be suitable for use in treating diseases/conditions which are associated with PTC mutations. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in treating conditions or disorders which are associated with PTC mutations in a subject.