2-Bromopyridine (I) is metalated by means of butyllithium and subsequently condensed with diethyl oxalate (II) to produce the keto ester adduct (III). Reaction of (III) with hot diethylaminosulfur trifluoride gives rise to the difluoro ester (IV), which is further reduced to alcohol (V) employing NaBH4 in EtOH. Treatment of (V) with triflic anhydride and 2,6-di-t-butyl-4-methylpyridine in CH2Cl2 yields the corresponding triflate (VI), which is then converted into azide (VII) by reaction with NaN3 in DMF. The pyridine ring of (VII) is oxidized by means of m-chloroperbenzoic acid to produce the N-oxide (VIII). Then, azido group reduction with PPh3 in moist THF leads to the primary amine (IX)

Acylation of glycine ethyl ester (X) with ethyl oxalyl chloride (XI) provides the oxalic acid mono-amide (XII). Subsequent condensation of (XII) with aminoacetaldehyde dimethylacetal (XIII) affords the diamide (XIV). Cyclization of (XIV) under acetal hydrolysis conditions leads to pyrazinone (XV). This is then brominated to (XVI) employing POBr3 in refluxing dichloroethane. Condensation of the bromopyrazinone (XVI) with amine (IX) at 120 C in a sealed vessel furnishes the aminopyrazinone (XVII). After chlorination of (XVII) with N-chlorosuccinimide, the resultant chloropyrazine ester (XVIII) is hydrolyzed to acid (XIX) under alkaline conditions

2-Bromo-4-chlorobenzoic acid (XX) is esterified to (XXI) employing methanolic HCl. Displacement of the 2-bromo group of (XXI) with Zn(CN)2 produces nitrile (XXII). Simultaneous reduction of both ester and cyano groups of (XXII) by means of LiAlH4 leads to amino alcohol (XXIII), which is further protected as the N-Boc derivative (XXIV) with di-tert-butyl dicarbonate. Treatment of the benzylic alcohol (XXIV) with diphenylphosphoryl azide affords the alkyl azide (XXV). After reduction of (XXV) to the corresponding amine (XXVI) by means of PPh3 in THF/H2O, coupling with carboxylic acid (XIX) with EDC, HOAt and Et3N furnishes amide (XXVII). The N-Boc group of (XXVII) is finally cleaved under acidic conditions to provide the title compound (1,2).

2-Bromo-4-chlorobenzoic acid (XX) is esterified to (XXI) employing methanolic HCl. Displacement of the 2-bromo group of (XXI) with Zn(CN)2 produces nitrile (XXII). Simultaneous reduction of both ester and cyano groups of (XXII) by means of LiAlH4 leads to amino alcohol (XXIII), which is further protected as the N-Boc derivative (XXIV) with di-tert-butyl dicarbonate. Treatment of the benzylic alcohol (XXIV) with diphenylphosphoryl azide affords the alkyl azide (XXV). After reduction of (XXV) to the corresponding amine (XXVI) by means of PPh3 in THF/H2O, coupling with carboxylic acid (XIX) with EDC, HOAt and Et3N furnishes amide (XXVII). The N-Boc group of (XXVII) is finally cleaved under acidic conditions to provide the title compound (1,2).