Hydrochloric Acid → HCID 131714732, compound

HRID 1982315Notes

Reaction equation

HRID 1982315 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].[ClH:23].[NH2:24][C@H:25]([C:33]([N:35]1[CH2:64][CH2:63][CH2:62][C@H:36]1[C:37]([NH:39][C@H:40]([C:48]([NH:50][C@H:51]([C:58]([O:60][CH3:61])=[O:59])[CH2:52][C:53]1[N:57]=[CH:56][NH:55][CH:54]=1)=[O:49])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:38])=[O:34])[CH2:26][CH2:27][CH2:28][NH:29][C:30](=[NH:32])[NH2:31].[C:65]1([NH2:76])[C:70]([F:71])=[C:69]([F:72])[C:68]([F:73])=[C:67]([NH2:74])[C:66]=1[F:75].Cl.Cl.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.O1CCOCC1.O>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([NH:24][C@H:25]([C:33]([N:35]1[CH2:64][CH2:63][CH2:62][C@H:36]1[C:37]([NH:39][C@H:40]([C:48]([NH:50][C@H:51]([C:58]([O:60][CH3:61])=[O:59])[CH2:52][C:53]1[N:57]=[CH:56][NH:55][CH:54]=1)=[O:49])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:38])=[O:34])[CH2:26][CH2:27][CH2:28][NH:29][C:30](=[NH:31])[NH2:32])=[O:12])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].[C:65]1([NH2:76])[C:70]([F:71])=[C:69]([F:72])[C:68]([F:73])=[C:67]([NH2:74])[C:66]=1[F:75].[ClH:23].[ClH:23].[CH3:2][C:10]([O-:12])=[O:11]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 178501416HCID 178501416, compoundHCID 178512917HCID 178512917, compound

Product 2

HCID 131714732HCID 131714732, compoundHCID 178501414HCID 178501414, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

1.27 g of Z-Arg-OH are dissolved in 20 ml of DMF and 240 μl of a 5N solution of HCl in dioxan while heating gently. After the addition of 1.9 g of H-Arg-Pro-Phe-His-OMe (in the form of the dihydrochloride) and 0.45 g of HOBt×H2O, the whole is cooled to 0° and then 0.85 g of DCCI in solid form is added. After the latter has dissolved, the whole is left to stand for 8 hours in an ice bath and for 1 day at room temperature and the precipitated DCH is filtered off. The filtrate is concentrated to approximately 5 ml and, from this, the peptide is precipitated by the addition of 50 ml of diisopropyl ether and dried. It is dissolved in 45 ml of methanol/glacial acetic acid/H2O (94:3:3), heated for 1 hour at 60°, again concentrated to approximately 5 ml and precipitated with diisopropyl ether and dried. The crude product is purified by chromatography over 120 g of silica gel (60, Merck, 230-400 mesh) using as eluant chloroform/methanol/H2O/glacial acetic acid (140:80:20:1). The pure fractions are combined, concentrated almost to dryness, dissolved in H2O and lyophilised, yielding Z-Arg-Arg-Pro-Phe-His-OMe in the form of the dihydrochloride-monoacetate; Rf (C)=0.4; Rf (E)=0.3.

Workup

  1. temperaturethe whole is cooled to 0°
  2. dissolutionAfter the latter has dissolved
  3. waitthe whole is left
  4. filtrationthe precipitated DCH is filtered off
  5. concentrationThe filtrate is concentrated to approximately 5 ml
  6. customfrom this, the peptide is precipitated by the addition of 50 ml of diisopropyl ether
  7. customdried
  8. dissolutionIt is dissolved in 45 ml of methanol/glacial acetic acid/H2O (94:3:3)
  9. temperatureheated for 1 hour at 60°
  10. concentrationagain concentrated to approximately 5 ml
  11. customprecipitated with diisopropyl ether
  12. customdried
  13. customThe crude product is purified by chromatography over 120 g of silica gel (60, Merck, 230-400 mesh)
  14. concentrationconcentrated almost to dryness
  15. dissolutiondissolved in H2O

Sources & evidence

ORD record
ord-38e05c651d2a4e488daee223452364e6
Source dataset
uspto-grants-1986_06
Patent number
US04595677

Reaction notes

Loading…