Hydrochloric Acid → HCID 178472803, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of 1.165 g. of L-pyroglutamyl-L-histidyl-L-tryptophanyl hydrazide (prepared as described in Example 1(b) above) in 30 ml. of N,N-dimethylformamide, cooled to -20° C., is added 6.13 ml. of 2.45 N hydrogen chloride in tetrahydrofuran and 0.5 ml. of isoamyl nitrite, and the resulting mixture is stirred at -10° to -20° C. for one hour. The mixture, which contains L-pyroglutamyl-L-histidyl-L-tryptophanyl azide, is next cooled to -50° C. and to it are added first 2.1 ml. of triethylamine, then 975 mg. of L-seryl-L-tyrosylglycine ethyl ester hydrochloride (prepared as described in (b) above), and finally 0.35 ml. more of triethylamine. The stirred mixture is allowed to warm to 0° C. during one hour and is kept at -5° C. for 21 hours. It is then filtered, and the filtrate is evaporated under reduced pressure to give a residue of L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosylglycine ethyl ester, which is dissolved in 50 ml. of methanol. To the solution is added 2 ml. of 99% hydrazine hydrate, and the resulting mixture is kept at room temperature for 16 hours. The solid that forms is isolated by filtration and stirred well with 20 ml. of water. The aqueous mixture is heated on the steam bath for 20 minutes, filtered, and the isolated solid is mixed with 15 ml. of methanol. The methanolic mixture is heated on the steam bath for 15 minutes, and the solid product is again isolated by filtration and dried. It is L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosylglycyl hydrazide monohydrate; m.p. 218°-220° C.; [α]D25 -22.7° (1% in 1 N hydrochloric acid).

Provenance & Evidence