合成路线1

6) The chiral piperazine (VII) can be obtained by several different ways: 6a) The sequential protection of piperazine-2(S)-carboxylic acid (XXIX) gives 1-(benzyloxycarbonyl)-4-(tert-butoxycarbonyl)piperazine-2(S)-carboxylic acid (XXX), which is condensed with tert-butylamine by means of EDC and HOBt to afford the tert-butylamide (XXXI). Finally, this compound is selectively deprotected by hydrogenation with H2 over Pd/C in methanol, yielding the chiral piperazine (VII). 6b) The partial hydrogenation of N-tert-butylpyrazine-2-carboxamide (XXXII) with H2 over Pd/C gives the tetrahydro derivative (XXXIII), which is sequentially protected as usual to the 1-(benzyloxycarbonyl)-4-(tert-butoxycarbonyl)-1,4,5,6-tetrahydropyrazin e -2-carboxamide (XXXIV). Finally, this compound is hydrogenated using the chiral catalyst [R-BINAP(COD)Rh]OTf to afford the chiral piperazine (XXXI), already obtained. 6c) The N-tert-butylpyrazine-2-carboxamide (XXXII) is fully reduced with H2 over Pd/C in propanol, giving the racemic N-tert-butylpiperazine-2-carboxamide (XXXV), which is submitted to optical resolution with (S)-(+)-camphosulfonic acid, yielding the (S)-isomer (XXXVI), which is then selectively protected with tert-butoxycarbonyl anhydride to give the desired chiral amide (VII).