The condensation of N-(benzyloxycarbonyl)-N-methyl-L-valine (I) with L-proline methyl ester (II) by means of pivaloyl chloride and triethylamine gives the dipeptide (III), which is deprotected with H2 over Pd/C in methanol yielding N-methyl-L-valyl-L-proline methyl ester (IV). The condensation of (IV) with N-(benzyloxycarbonyl)-L-valine N-carboxyanhydride (V) by means of DIEA in DMG affords the tripeptide (VI), which is deprotected by hydrogenation over Pd/C in methanol giving L-valyl-L-(N-methyl)valyl-L-proline methyl ester (VII). A new condensation of (VII) with (V) yields the tetrapeptide (VIII), which is hydrolyzed with LiOH in methanol affording N-(benzyloxycarbonyl)-L-valyl-L-valyl-L-(N-methyl)valyl-L-proline (IX), which is condensed with L-proline tert-butylamide (X) by means of NMM and EDC in dichloromethane giving the pentapeptide (XI), which is deprotected with H2 over Pd/C in methanol and reductomethylated with formaldehyde and H2 over Pd/C in the same solvent.

The condensation of N-(benzyloxycarbonyl)-N-methyl-L-valine (I) with L-proline methyl ester (II) by means of pivaloyl chloride and triethylamine gives the dipeptide (III), which is deprotected with H2 over Pd/C in methanol yielding N-methyl-L-valyl-L-proline methyl ester (IV). The condensation of (IV) with N-(benzyloxycarbonyl)-L-valine N-carboxyanhydride (V) by means of DIEA in DMG affords the tripeptide (VI), which is deprotected by hydrogenation over Pd/C in methanol giving L-valyl-L-(N-methyl)valyl-L-proline methyl ester (VII). A new condensation of (VII) with (V) yields the tetrapeptide (VIII), which is hydrolyzed with LiOH in methanol affording N-(benzyloxycarbonyl)-L-valyl-L-valyl-L-(N-methyl)valyl-L-proline (IX), which is condensed with L-proline tert-butylamide (X) by means of NMM and EDC in dichloromethane giving the pentapeptide (XI), which is deprotected with H2 over Pd/C in methanol and reductomethylated with formaldehyde and H2 over Pd/C in the same solvent.