Hydrochloric Acid → HCID 178501374, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 932 mg. of L-pyroglutamyl-L-histidyl-L-tryptophanyl hydrazide (prepared as described in (b) above) in a mixture of 8.4 ml. of dry N,N-dimethylformamide and 7.0 ml. of dimethyl sulfoxide, cooled to -12° C., is added dropwise 5.16 ml. of 2.325 N hydrogen chloride in tetrahydrofuran. The mixture is cooled to -20° C., 0.4 ml. of isoamyl nitrite is added, and the resulting mixture is stirred at -20° C. for 30 minutes. The mixture, which contains L-pyroglutamyl-L-histidyl-L-tryptophanyl azide, is cooled to -25° C., and to it are added first 1.96 ml. of triethylamine and then 636 mg. of L-seryl-L-tyrosine methyl ester hydrochloride (prepared as described in (c) above). The reaction mixture is stirred at -20° C. for 30 minutes and at 0° C. for 30 minutes and is stored in a refrigerator at -5° C. for 48 hours. It is then filtered and the filtrate is evaporated under reduced pressure. The residue is triturated with tetrahydrofuran, the mixture is stored in the refrigerator for 26 hours, and the solvent is decanted to give a residue of L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosine methyl ester, which is dissolved in 20 ml. of methanol. To the solution is added 1 ml. of 99% hydrazine hydrate, and the mixture is stirred at room temperature overnight to give solid L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosyl hydrazide, which is isolated by filtration and dried under reduced pressure; m.p. 215°-217° C., following crystallization from water; [α]D25 -17° (1.01% in N,N-dimethylformamide).

Provenance & Evidence