Hydrochloric Acid → HCID 178501374, compound

HRID 65595Notes

Reaction equation

HRID 65595 reaction equation
Cl.N(OCCC(C)C)=O.[NH:10]1[C:14](=[O:15])[CH2:13][CH2:12][C@H:11]1[C:16]([NH:18][C@H:19]([C:26]([NH:28][C@H:29]([C:40]([N:42]=[N+]=[N-])=[O:41])[CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)=[O:27])[CH2:20][C:21]1[N:25]=[CH:24][NH:23][CH:22]=1)=[O:17].Cl.[CH3:46][O:47][C:48](=[O:65])[C@H:49]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([OH:64])=[CH:60][CH:59]=1)[NH:50][C:51](=[O:56])[C@H:52]([CH2:54][OH:55])N>O1CCCC1.C(N(CC)CC)C.CS(C)=O.CN(C)C=O>[CH3:46][O:47][C:48](=[O:65])[C@H:49]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([OH:64])=[CH:60][CH:59]=1)[NH:50][C:51](=[O:56])[C@H:52]([CH2:54][OH:55])[NH:42][C:40](=[O:41])[C@H:29]([CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)[NH:28][C:26](=[O:27])[C@H:19]([CH2:20][C:21]1[N:25]=[CH:24][NH:23][CH:22]=1)[NH:18][C:16](=[O:17])[C@@H:11]1[CH2:12][CH2:13][C:14](=[O:15])[NH:10]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 70166468HCID 70166468, compoundHCID 178514637HCID 178514637, compound

Product 1

HCID 178501374HCID 178501374, compound

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

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).

Workup

  1. additionis added dropwise 5.16 ml
  2. temperatureis cooled to -25° C.
  3. additionto it are added first 1.96 ml
  4. stirringThe reaction mixture is stirred at -20° C. for 30 minutes and at 0° C. for 30 minutes
  5. waitis stored in a refrigerator at -5° C. for 48 hours
  6. filtrationIt is then filtered
  7. customthe filtrate is evaporated under reduced pressure
  8. customThe residue is triturated with tetrahydrofuran
  9. waitthe mixture is stored in the refrigerator for 26 hours
  10. customthe solvent is decanted

Sources & evidence

ORD record
ord-11c3a27739e64a668bc59bf50f183ad7
Source dataset
uspto-grants-1978_12
Patent number
US04128540

Reaction notes

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