Preparation of Morpholino-Ester 15. The optimized preparation of compound 10 is described below. The readily available 2-chloroisonicotinic acid 13 was first transformed to the corresponding tert-butyl ester using Boc2O and triethylamine in the presence of catalytic amount of DMAP in NMP to generate tert-butyl 2-chloroisonicotinate 14 in 91% corrected isolated yield. The formation of the tBu ester was found to be beneficial for several reasons: a) to ease the isolation of each intermediate, b) minimize losses due to the zwitterionic properties of isonicotinic acid related species, c) to avoid incompatibilities with the organometallic species downstream (requiring extra organometallic reagent among other) and d) to prevent the formation of non-negligible amounts of morpholine amide during the SNAr reaction of the free carboxylic acid moiety in the presence of morpholine (see . The SNAr between compound 4 and morpholine was investigated in various solvents and bases, organic and inorganic. Interestingly, it was found that the reaction in morpholine as solvent, where it acts both as nucleophile and base, gave the best result. Compound 14 could be treated with morpholine to generate the corresponding tert-butyl 2-morpholinoisonicotinate 15 in 97% corrected isolated yield.