The condensation of resin bounded L-phenylalanine (I) with N-(tert-butoxycarbonyl)-L-phenylalanine (II) by means of 1,3-diisopropylcarbodiimide (DIC) and HOBT gives the protected, resin bounded dipeptide (III), which is deprotected with TFA to yield the dipeptide (IV). The reductocondensation of (IV) with 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carbaldehyde (V) by means of NaBH3CN affords the protected pseudo tripeptide (VI), which is deprotected with TFA as before yielding the pseudo tripeptide (VII). The condensation of (VII) with the protected L-dimethyltyrosine (VIII) by means of DIC and HOBT affords the protected resin bounded seudotetrapeptide (IX), which is deprotected with TFA as before giving the resin bounded seudotetrapeptide (X). Finally, the target seudotetrapeptide is cleaved from the resin by means of HF and anisole.
The intermediate 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carbaldehyde (V) has been obtained as follows: The reaction of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (XI) with N,O-dimethylhydroxylamine (XII) by means of BOP gives the corresponding N-methoxy-N-methylamide (XIII), which the reduced to the target aldehyde (V) with LiAlH4.