Hydrochloric Acid → HCID 178476726, compound

HRID 1833324Notes

Reaction equation

HRID 1833324 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:17]([NH:19]N)=[O:18])[CH2:11][C:12]1[N:16]=[CH:15][NH:14][CH:13]=1)=[O:8].Cl.N(OCCC(C)C)=[O:23].Cl.N1[CH2:43][CH2:42][CH2:41][C@H:32]1[C:33]([NH:35][CH2:36][CH2:37][C:38]([NH2:40])=[O:39])=[O:34]>CS(C)=O.CN(C)C=O.O1CCCC1.C(N(CC)CC)C>[C:17]([OH:18])(=[O:23])[CH3:10].[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:17]([N:19]1[CH2:43][CH2:42][CH2:41][C@H:32]1[C:33]([NH:35][CH2:36][CH2:37][C:38]([NH2:40])=[O:39])=[O:34])=[O:18])[CH2:11][C:12]1[N:16]=[CH:15][NH:14][CH:13]=1)=[O:8]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8053Isoamyl NitriteHCID 7061593365983-44-0HCID 178514449HCID 178514449, compound

Product 1

HCID 178476726HCID 178476726, compound

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
-20 °C

Procedure

A suspension of 7.64 g of L-pyroglutamyl-L-histidine hydrazide in a mixture of 95 ml of dimethyl sulphoxide and 125 ml of dimethylformamide was treated at -20° C with 104 ml of 1.64-N HCl in tetrahydrofuran. 5 ml of isoamyl nitrite were added to this solution. The mixture was stirred for 30 minutes at -20° C, cooled to -30° C and neutralised at this temperature with 23.7 ml of triethylamine. 7.7 g of L-prolyl-β-alaninamide hydrochloride were dissolved in a mixture of 20 ml of dimethyl sulphoxide and 15 ml of dimethylformamide. cooled to -10° C, neutralised with 4.9 ml of triethylamine and added to the previously described mixture. The thus-obtained mixture was stirred for 1 hour at -20° C, stored for 24 hours at 4° C and filtered. The filtrate was concentrated in vacuo, the residue taken up in 350 ml of water and extracted five times with 70 ml of ethyl acetate each time. The aqueous phase was concentrated in vacuo and the residue purified by countercurrent distribution in 1-butanol/glacial acetic acid/water (4:1:5). L-pyroglutamyl-L-histidyl-L-prolyl-β-alaninamide acetate was obtained by concentration of the appropriate fractions in vacuo and subsequent lyophilisation. [α]D25 = -83.4° (c = 1 in 1 N acetic acid).

Workup

  1. temperaturecooled to -10° C
  2. additionadded to the previously described mixture
  3. stirringThe thus-obtained mixture was stirred for 1 hour at -20° C
  4. waitstored for 24 hours at 4° C
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. extractionextracted five times with 70 ml of ethyl acetate each time
  8. concentrationThe aqueous phase was concentrated in vacuo
  9. customthe residue purified by countercurrent distribution in 1-butanol/glacial acetic acid/water (4:1:5)

Sources & evidence

ORD record
ord-d7f99f1282ba42deb4ca7d28dafaed64
Source dataset
uspto-grants-1978_01
Patent number
US04066635

Reaction notes

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