Hydrochloric Acid → HCID 178501440, Verbindung

Temperatur

-20 °C

To a suspension of 7.0 g. of L-pyroglutamyl-L-histidyl-L-tryptophanyl hydrazide (prepared as described in Example 1(b) above) in 180 ml. of N,N-dimethylformamide, cooled to -15° C., is added dropwise 36.5 ml. of 2.51 N hydrogen chloride in tetrahydrofuran. The mixture is cooled to -20° C., 3.04 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 next cooled to -30° C., and to it are added first 14.84 ml. of triethylamine, dropwise, and then 7.34 g. of L-seryl-L-tyrosylglycyl-L-leucine 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 2 hours and is then stored in the refrigerator at -5° C. overnight. It is then filtered, and the filtrate is evaporated. The residue is triturated with 250 ml. of tetrahydrofuran, and after 3 hours at room temperature, the solid residue of L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosylglycyl-L-leucine methyl ester is isolated by filtration and dissolved in 650 ml. of methanol. The methanolic solution is treated with activated charcoal and filtered, and to the filtrate is added 15.0 ml. of 99% hydrazine hydrate. The resulting mixture is kept at room temperature for 3 days, and the solid that forms is isolated and mixed with 200 ml. of ether. After 2 days at room temperature, the ethereal mixture is filtered, and the isolated solid is mixed with 360 ml. of methanol. The methanolic mixture is heated to boiling for 5 minutes, kept at room temperature for 10 minutes, and filtered to give a solid product, which is washed with methanol and with ether and dried. It is L-pyroglutamyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosylglycyl-L-leucyl hydrazide dihydrate; m.p. 213°-215° C.; [α]D25 -21.2° (1.93% in a 1:1 mixture of N,N-dimethylformamide and dimethyl sulfoxide).

1. additionTo a suspension of 7.0 g
2. additionis added dropwise 36.5 ml
3. temperatureis next cooled to -30° C.
4. additionto it are added first 14.84 ml
5. stirringThe reaction mixture is stirred at -20° C. for 30 minutes and at 0° C. for 2 hours
6. waitis then stored in the refrigerator at -5° C. overnight
7. filtrationIt is then filtered
8. customthe filtrate is evaporated
9. customThe residue is triturated with 250 ml
10. waitof tetrahydrofuran, and after 3 hours at room temperature

ORD-Eintrag

ord-f191a6a0c5f74e58b0ec7520e81b8b0a

Quelldatensatz

uspto-grants-1978_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04128540