Patent ID: 7612209

Claim:
A process for the manufacture of the compounds of formula I: wherein: (1) R 1 is a side chain of an alpha amino acid, (2) R 2 is an amino protecting group, (3) R 3 and R 4 are independently either hydrogen or a C 1-4 -alkyl, and (4) R 5 is hydrogen or methyl; wherein said process comprises the following steps: (a) reacting an amino acid derivative of formula II: wherein R 1 and R 2 are as defined previously, with serine or threonine to obtain a dipeptide of formula III: wherein R 1 , R 2 and R 5 are as defined previously; (b) adding the amine of formula V: wherein R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen, a C 1-4 -alkyl and a C 3-7 -cycloalkyl, with the proviso that not all of R 6 , R 7 and R 8 are hydrogen; to form the ammonium salt of the dipeptide of formula III in crystal form: wherein R 1 , R 2 , R 5 , R 6 , R 7 and R 8 are as defined previously; (c) adding an acid to the ammonium salt in step (b) to release the free acid of the dipeptide of formula III from the ammonium salt, and removing the protonated amine from the reaction mixture; and (d) effecting the ring closure of the free acid of the dipeptide of formula III in step (c) with a compound selected from the group consisting of: wherein: (1) R 3 and R 4 are independently either hydrogen or a C 1-4 -alkyl, with the proviso that not both R 3 and R 4 are hydrogen, (2) R 9a and R 9b are independently a C 1-4 -alkyl, (3) R 10 is a C 1-4 -alkyl, a C 1-4 -alkanoyl or an aryl, and (4) R 11 is hydrogen or a C 1-3 -alkyl, in the presence of an acidic catalyst to obtain compounds of formula I.