Alkylation of azaglycine derivatives

A process for the preparation of an alkylated azaglycine derivative of the formula I

• X--(A).sub.n --N(R)--NH--CO--NH.sub.2 (I)
• in which
• X is an amino protective group wherein said protective group is Fmoc, Boc or Z;
• or X is C.sub.1 -C.sub.8 -alkanoyl, C.sub.6 -C.sub.14 -arylcarbonyl or C.sub.6 -C.sub.14 -aryl-C.sub.1 -C.sub.4 -alkanoyl;
• A is an .alpha.-amino acid or an .alpha.-amino acid radical whose amino group is monosubstituted, on the third function, when present, A is optionally protected;
• n is 0-10, X being C.sub.1 -C.sub.8 -alkanoyl, C.sub.6 -C.sub.14 -arylcarbonyl or C.sub.6 -C.sub.14 -aryl-C.sub.1 -C.sub.4 -alkanoyl if n=O;
• and
• R is C.sub.1 -C.sub.18 -alkyl, C.sub.6 -C.sub.14 -aryl-C.sub.1 -C.sub.4 -alkyl, C.sub.5 -C.sub.7 -heteroaryl, or pyridyl C.sub.1 -C.sub.4 -alkyl wherein heteroaryl does not contain an acidic-NH group, and wherein said C.sub.6 -C.sub.14 -aryl-C.sub.1 -C.sub.4 -alkyl, C.sub.5 -C.sub.7 -heteroaryl, or pyridyl C.sub.1 -C.sub.4 -alkyl are optionally substituted in the aromatic ring by a halogen, a C.sub.1 -C.sub.6 alkyl or a C.sub.1 -C.sub.6 alkoxy;
• which comprises reacting a compound of the formula II
• X--(A).sub.n --NH--NH--CO--NH.sub.2 (II)
• in which X, A and n have the above mentioned meanings, with a primary or secondary C.sub.1 -C.sub.18 -alkylalkanol, a C.sub.6 -C.sub.14 -aryl-C.sub.1 -C.sub.4 -alkanol, a C.sub.5 -C.sub.7 -heteroaryl alcohol or a pyridyl C.sub.1 -C.sub.4 alkanol, wherein said heteroaryl does not contain an acetic-NH group and wherein said C.sub.6 -C.sub.14 aryl-C.sub.1 -C.sub.4 alkanol, C.sub.5 -C.sub.7 heteroaryl alcohol and pyridyl C.sub.1 -C.sub.4 alkanol are optionally substituted in the aromatic ring by a halogen, a C.sub.1 -C.sub.6 alkyl or a C.sub.1 -C.sub.6 alkoxy, and excess DEAR, and a tri-C.sub.1 -C.sub.6 -alkylphosphine, tri-C.sub.6 -C.sub.14 -arylphosphine or pyridyl-di-C.sub.6 -C.sub.14 -arylphosphine, it being possible for the aryl moiety to be optionally substituted by di-C.sub.1 -C.sub.4 -alkylamino, in an ether at 0.degree. C. to 30.degree. C., and removing the amino protective group X, with the proviso that X is not Fmoc when tri-n-butylphosphine is used.