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

HRID 1846414Notes

Reaction equation

HRID 1846414 reaction equation
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

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

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.

Workup

  1. customwere prepared

Sources & evidence

ORD record
ord-84ad363825544510b8c17be2c5968cdb
Source dataset
uspto-grants-2015_02
Patent number
US08952032B2

Reaction notes

Loading…