合成路线1

In a different procedure, the acyclic tetraamine (IX) is protected with p-toluenesulfonyl chloride to afford a separable mixture of ditosyl (X) and tritosyl compounds (XI). Condensation of (X) with p-dibromoxylene (IIIa) provides the tetratosyl dimer (XII), which is further tosylated to (XIII) by means of p-toluenesulfonyl chloride and K2CO3. Alternatively, the hexatosyl dimer (XIII) can be obtained by condensation of the trisulfonylated tetraamine (XI) with p-dibromoxylene (IIIa) in the presence of N,N-diisopropylethylamine. Ring closure of (XIII) to furnish the bis-macrocycle (IV) is then accomplished by reaction with ethylene glycol ditosylate (XIV) in the presence of Cs2CO3 or under phase-transfer conditions. Subsequent acidic deprotection of (IV) gives the target compound (7). In a related approach, the open-chain tetraamine (IX) is protected with ethyl trifluoroacetate and N,N-diisopropylethylamine to afford the triacyl derivative (XV) as the main product, which is further condensed with dibromide (IIIa), yielding the trifluoroacetyl-protected dimer (XVI). The hexatrifluoroacetyl compound (XVI) is then converted to the hexatosyl analogue (XIII) by alkaline amide hydrolysis, followed by treatment with p-toluenesulfonyl chloride. Ring closure of (XIII) with ethylene glycol ditosylate (XIV) and subsequent acidic deprotection as above gives plerixafor (8, 9). Scheme 2.