US 2026/0167668 A1 · PROCESS FOR THE PREPARATION OF FMOC-GLY-THR [PSI (ME, ME) PRO]-OH

Abstract

Disclosed is a process for the preparation of Fmoc-Gly-Thr [Psi (Me, Me) pro]-OH by reacting Fmoc-glycyl chloride with N, O-Bis(trimethylsilyl)-threonine trimethylsilyl ester, in the presence of a base, to obtain Fmoc-Gly-(O-trimethylsilyl)-threonine trimethylsilyl ester, which on acid hydrolysis gives Fmoc-Gly-Thr-OH. Cyclization of Fmoc-Gly-Thr-OH using 2-methoxy propene or 2,2-dimethoxypropane in the presence of pyridinium p-toluene sulfonate as the acid catalyst, in 2-methyltetrahydrofuran, results in Fmoc-Gly-Thr [Psi (Me, Me) pro]-OH. Direct cyclization of Fmoc-Gly-(O-trimethylsilyl)-L-Threonine-trimethylsilyl ester in a similar manner also gives Fmoc-Gly-Thr [Psi (Me, Me) pro]-OH.

Claims10

Dependent claims

A process for the preparation of Fmoc-Gly-Thr [Psi (Me, Me) pro]-OH having the formula (I):

comprising:
(a) reacting Fmoc-glycyl chloride having the formula (II),
with N, O— Bis(trimethylsilyl)-L-threonine trimethylsilyl ester having the formula (III), in a presence of a base in a non-aqueous organic solvent,
(b) treating a solution containing a reaction mixture from step (a) with water followed by aqueous hydrochloric acid resulting in, at a biphasic surface, precipitation of Fmoc-Gly-Thr-OH (IV), and
(c) reacting Fmoc-Gly-Thr-OH (IV) with a cyclizing agent, using 2-methyltetrahydro-furan as a solvent, at a temperature of 45° C. to 75° C. in a presence of an acid catalyst to provide Fmoc-Gly-Thr [Psi (Me, Me) pro]-OH of the formula (I).

2 more elements

Dependencies are inferred from the claim text.

Process for the preparation of fmoc-gly-thr [psi (me, me) pro]-oh

Life of this patent

Process for the preparation of fmoc-gly-thr [psi (me, me) pro]-oh

Life of this patent

Abstract

Claims10