合成路线1

The aminoazepinone building block (III) can be prepared as follows. 2,4-Dimethoxybenzylamine (XIII) is alkylated with 2,3-dibromopropene (XIV) in the presence of Et3N to yield amine (XV), which is condensed with 2(R)-(benzyloxycarbonylamino)-4-pentenoic acid (XVI) by means of EDC in CH2Cl2 giving amide (XVII). Subsequent coupling of vinyl bromide (XVII) with 2,3-difluorophenylboronic acid (XVIII) in the presence of 1,1’-bis(diphenylphosphino)ferrocenedichloropalladium(II)· CH2Cl2 and Na2CO3 in DMF gives (XIX). Ring-closing olefin metathesis in diene (XIX) utilizing a second-generation Grubbs catalyst generates the azepinone derivative (XX), from which the dimethoxybenzyl group is removed by means of trifluoroacetic acid in CH2Cl2 to provide compound (XXI). Hydrogenation of olefin (XXI) and simultaneous Cbz group cleavage in the presence of Pd/C and Boc2O leads to the Boc-protected aminoperhydroazepinone (XXII). After alkylation of lactam (XXII) with the 2,2,2-trifluoroethyl sulfonate (XXIII) and NaH in DMF, the N-Boc group is removed using trifluoroacetic acid to furnish the target amine (III) (1). Scheme 2.