Hydrochloric Acid → HCID 178468103, compound

HRID 2398510Notes

Reaction equation

HRID 2398510 reaction equation
[NH2:1][C@H:2]([C:8]([NH:10][C@H:11]([C:18]([NH:20][C@H:21]([C:32]([NH:34]N)=[O:33])[CH2:22][C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[NH:25][CH:24]=1)=[O:19])[CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1)=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[OH:6].Cl.[O:37]1CCOCC1.N[C@H:44]([C:47]([NH:49][C@H:50]([C:59]([NH:61][C@@H:62]([C:69]([NH:71][C@H:72]([C:77]([NH:79][C@H:80]([C:88]([N:90]1[CH2:99][CH2:98][CH2:97][C@H:91]1[C:92]([NH:94][CH2:95][CH3:96])=[O:93])=[O:89])[CH2:81][CH2:82][CH2:83][NH:84][C:85](=[NH:87])[NH2:86])=[O:78])[CH2:73][CH:74]([CH3:76])[CH3:75])=[O:70])[CH2:63][O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:60])[CH2:51][C:52]1[CH:57]=[CH:56][C:55]([OH:58])=[CH:54][CH:53]=1)=[O:48])[CH2:45][OH:46].Cl.C(N1CCOCC1)C>CN(C)C=O.O1CCOCC1>[NH2:1][C@H:2]([C:8]([NH:10][C@H:11]([C:18]([NH:20][C@H:21]([C:32]([NH:34][C@H:44]([C:47]([NH:49][C@H:50]([C:59]([NH:61][C@@H:62]([C:69]([NH:71][C@H:72]([C:77]([NH:79][C@H:80]([C:88]([N:90]1[CH2:99][CH2:98][CH2:97][C@H:91]1[C:92]([NH:94][CH2:95][CH3:96])=[O:93])=[O:89])[CH2:81][CH2:82][CH2:83][NH:84][C:85](=[NH:86])[NH2:87])=[O:78])[CH2:73][CH:74]([CH3:76])[CH3:75])=[O:70])[CH2:63][O:64][C:65]([CH3:67])([CH3:68])[CH3:66])=[O:60])[CH2:51][C:52]1[CH:53]=[CH:54][C:55]([OH:58])=[CH:56][CH:57]=1)=[O:48])[CH2:45][OH:46])=[O:33])[CH2:22][C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[NH:25][CH:24]=1)=[O:19])[CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1)=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[OH:6].[CH3:2][C:3]([CH2:4][C:5]([OH:6])=[O:7])=[O:37]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7525EthylmorpholineHCID 204431481,4-Dioxane hydrochlorideHCID 178465158HCID 178465158, compoundHCID 178514448HCID 178514448, compound

Product 1

HCID 178468103HCID 178468103, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 500 mg of Glu-His-Trp-NH-NH2 in 6 ml of dimethyl formamide were added, at -30° C, 0.66 ml of a 6.05 N HCl/dioxane solution and 1.2 ml of a 10% tert.-butyl nitrile solution in absolute dioxane. The solution was stirred for 20 minutes at -10° C and 877.8 mg of crude H-Ser-Tyr-D-Ser(But)-Leu-Arg-Pro-NH-C2H5 . 2 HCl and 0.78 ml of N-ethyl morpholine were added at -40° C. The mixture was allowed to stand overnight at 4° C. It was concentrated and the residue was triturated with ether. The substance was dissolved in water and chromatographed over Dowex(R) 1×2 (acetate form). The eluate was concentrated and purified over a carboxymethyl cellulose column (90 × 1.5 cm), that was equilibrated with 0.002 m NH4 -acetate solution. The substance was added as a solution in a 0.002 m NH4 -acetate solution. It was eluted with a 0.002 m NH4 -acetate solution in which the gradient of a 0.1 m NH4 -acetate solution was established (mixed volume 250 ml).

Workup

  1. waitto stand overnight at 4° C
  2. concentrationIt was concentrated
  3. customthe residue was triturated with ether
  4. dissolutionThe substance was dissolved in water
  5. customchromatographed over Dowex(R) 1×2 (acetate form)
  6. concentrationThe eluate was concentrated
  7. custompurified over a carboxymethyl cellulose column (90 × 1.5 cm), that
  8. additionThe substance was added as a solution in a 0.002 m NH4 -acetate solution
  9. washIt was eluted with a 0.002 m NH4 -acetate solution in which the gradient of a 0.1 m NH4 -acetate solution
  10. addition(mixed volume 250 ml)

Sources & evidence

ORD record
ord-3f3f6a423f804477b61425369bf8c716
Source dataset
uspto-grants-1977_05
Patent number
US04024248

Reaction notes

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