Reaktion #81340

ord-afd2338aa08748c6bacca36696125a72

Reaktionsgleichung

CCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(C)C)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
TFA
CCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(C)C)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
N-(N-(N-(N-(1,1-Dimethylethoxycarbonyl)-L-alanyl)-L-alanyl)-L -prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester
CCN(C(C)C)C(C)C
diisopropylethylamine
O=C(Cl)N(c1ccccc1)c1ccccc1
diphenylcarbamoyl chloride
→
CCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)N(c2ccccc2)c2ccccc2)C(C)C)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
N-(N -(N-(N-(diphenylcarbamoyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna -1,4-dien-21-yl] ester
Ausbeute 97.0%

Edukte

CCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(C)C)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
TFA
CCC(=O)O[C@]1(C(=O)C(O)OC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(C)C)CC[C@H]2[C@@H]3C[C@H](C)C4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C
N-(N-(N-(N-(1,1-Dimethylethoxycarbonyl)-L-alanyl)-L-alanyl)-L -prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester
CCN(C(C)C)C(C)C
diisopropylethylamine
O=C(Cl)N(c1ccccc1)c1ccccc1
diphenylcarbamoyl chloride

Reagenzien

Keine

Lösungsmittel

ClCCl
dichloromethane

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Sonstigeafter removal of the solvent i.vac
  2. 2
    Sonstigeis chromatographed

Vorschrift

150 mg (0.17 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3) and 150 μl (0.89 mmol) of diisopropylethylamine are dissolved in 6 ml of dichloromethane, mixed with 155 mg (0.37 mmol) of diphenylcarbamoyl chloride and stirred for 110 hours at room temperature. The residue that remains after removal of the solvent i.vac. is chromatographed. Gradient chromatography (Lichroprep Si60A pre-packed column, hexane→hexane/dichloromethane/methanol 30:60:10) yields 158 mg (97%) of N-(N -(N-(N-(diphenylcarbamoyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna -1,4-dien-21-yl] ester, and after recrystallization, 112 mg (68%) in crystalline form from dichloromethane/diisopropyl ether.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05616573uspto-grants-1997_04