Butylmagnesium bromide (II) was added to the Weinreb amide of Boc-L-leucine (I), yielding ketone (III), which was further reduced with NaBH4 to give alcohol (IV) as a diastereomeric mixture. The Boc protecting group of (IV) was removed employing trifluoroacetic acid in CH2Cl2, and the resulting amino alcohol (V) was coupled with N-Boc-L-histidine (VI) by means of BOP reagent to afford amide (VII). Deprotection of the Boc group of (VII) with trifluoroacetic acid then furnished the target C-terminal fragment (VIII).

Azepinone (X) was obtained by cyclization of Boc-L-lysine (IX) in the presence of NaHCO3 and BOP reagent. Subsequent alkylation of the lactam nitrogen of (X) with benzyl bromoacetate (XI) afforded (XII). After Boc deprotection of (XII) with trifluoroacetic acid, coupling with Boc-L-alanine (XIII) gave dipeptide (XIV). This was subjected to a further deprotection and coupling sequence with Boc-L-tryptophan (XV) to give tripeptide (XVI), and then with Boc-L-glutamine (XVII), yielding (XVIII). Acid deprotection of the Boc group of (XVIII), followed by coupling with p-hydroxyphenylpropionic acid (XIX) provided the peptide amide (XX).

Deprotection of the benzyl ester group of the N-terminal fragment (XX) by hydrogenolysis provided carboxylic acid (XXI). This was finally coupled with the C-terminal fragment (VIII) employing BOP reagent to furnish the title peptide derivative.