Alkylation of 4-cyano-4'-hydroxybiphenyl (I) with 1-bromo-3-chloropropane (II) yields the chloropropyl ether (III). This is then condensed with the mono-protected homopiperazine (IV) to furnish (V). Removal of the N-Boc group of (V) to afford amine (VI) is then accomplished by treatment with trifluoroacetic acid in CH2Cl2. Amine (VI) is subsequently coupled with N-Boc-D-thiazolylalanine (VII) in the presence of EDC/DMAP producing amide (VIII). (1,2)
Acidic cleavage of the N-Boc group of (VIII) furnishes amine (IX). Finally, acylation of (IX) with 2-furoyl chloride (X) leads to the title compound. (1,2)
Intramolecular cyclization of p-hydroxy-4-chlorobutyrophenone (I) under alkaline conditions yields cyclopropyl(4-hydroxyphenyl) ketone (II). The phenolic hydroxyl group is then alkylated by 1-bromo-3-chloropropane (III) to furnish the chloropropyl ether (IV). Subsequent condensation of alkyl chloride (IV) with piperazine (V) gives rise to the N-substituted piperazine (VI). This is then coupled with N-Boc-L-alanine (VII) in the presence of EDC/DMAP to afford amide (VIII) (1, 2). After acidic cleavage of the N-Boc protecting group, the resultant monosubstituted piperazine (IX) is acylated by furanoyl chloride (X) to furnish the target furamide derivative
Cyclization of 4-chloro-4'-hydroxybutyrophenone (I) in the presence of 50% aqueous NaOH produces cyclopropyl (4-hydroxyphenyl) ketone (II). This is then alkylated with 1-bromo-3-chloropropane (III) to afford the chloropropyl ether (IV). Chloride displacement in (IV) with an excess of piperazine (V) in the presence of KI and K2CO3 furnishes the monosubstituted piperazine (VI). Subsequent coupling of piperazine (VI) with N-Boc-L-alanine (VII) leads to amide (VIII). Finally, Boc group cleavage in (VIII) employing trifluoroacetic acid yields the title compound (1-3).