合成路线1

The asymmetric 1,3-dipolar cycloaddition of the nitrile oxide resulting from 4-bromo-N-hydroxybenzenecarboximidoyl chloride (I) to allyl alcohol (II) in the presence of (R,R)-diisopropyl tartrate and diethylzinc afforded the (R)-5-(hydroxymethyl)isoxazoline (III). Treatment of 4-bromopyridine (IV) with hexamethylditin and dichlorobis(triphenylphosphine)palladium yielded 4-trimethylstannylpyridine (V). Subsequent coupling of bromophenylisoxazoline (III) with stannylpyridine (V) in the presence of tris(dibenzylideneacetone)-dipalladium and tri(2-furyl)phosphine gave rise to the pyridylphenylisoxazole (VI). After conversion of (VI) to the mesylate (VII), treatment with ammonium hydroxide in a sealed vessel provided primary amine (VIII). Finally, acetylation of (VIII) with Ac2O and pyridine furnished the title amide.