3-Aminophenol → N-(3-hydroxyphenyl)-N-(1-phenethylpiperidin-4-yl)propionamide

HRID 1046542

Reaktionsgleichung

Reaktionsgleichung von HRID 1046542
C(N1CC[C:12](=[O:15])[CH2:11][CH2:10]1)CC1C=CC=CC=1.NC1C=C(O)C=CC=1.[CH2:24]([N:32]1[CH2:37][CH2:36][CH:35]([NH:38][C:39]2[CH:40]=[C:41]([OH:45])[CH:42]=[CH:43][CH:44]=2)[CH2:34][CH2:33]1)[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(OC(=O)CC)(=O)CC.CN(C1C=CC=CN=1)C>C(N(CC)CC)C>[OH:45][C:41]1[CH:40]=[C:39]([N:38]([CH:35]2[CH2:34][CH2:33][N:32]([CH2:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:37][CH2:36]2)[C:12](=[O:15])[CH2:11][CH3:10])[CH:44]=[CH:43][CH:42]=1

Komponenten

7

Edukt 5

HCID 115683-Aminophenol2×HCID 218852-DimethylaminopyridineHCID 31263Propionic anhydrideHCID 96437N-Phenethyl-4-piperidinoneHCID 574239333-(1-Phenethylpiperidin-4-ylamino)phenol

Produkt 1

HCID 59200765N-(3-hydroxyphenyl)-N-(1-phenethylpiperidin-4-yl)propionamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

As indicated in Scheme 11-D above, the desired mPEGn-O-fentanyl conjugates were prepared by first reacting 1-phenethylpiperidin-4-one with 3-aminophenol under reducing conditions to thereby convert the keto functionality into an amine, i.e., by reaction with the amino group of 3-aminophenol. The product, 3-(1-phenethylpiperidin-4-ylamino)phenol, was then reacted with propionic anhydride in the presence of base (e.g., triethyl amine) and dimethylaminopyridine (DMAP) under conditions effective to form N-(3-hydroxyphenyl)-N-(1-phenethylpiperidin-4-yl)propionamide. Finally, introduction of the oligomeric PEG functionality was carried out by reacting the precursor, N-(3-hydroxyphenyl)-N-(1-phenethylpiperidin-4-yl)propionamide, with a molar excess of mPEGoligotosylate under coupling conditions effective to form the desired conjugates. Ratios of reactants and reaction conditions generally employed are provided in the reaction schemes above.

Aufarbeitung

  1. customwere prepared

Quellen und Nachweise

ORD-Eintrag
ord-220b22664a474815be6214db4599eb41
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569343B2

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