Ethanol → N-hydroxy-N'-methyl-2-[methyl({4'-[3-(morpholin-4-yl)propoxy]biphenyl-4-yl}carbonyl)amino]propanediamide

HRID 1519674Notes

Reaction equation

HRID 1519674 reaction equation
C(O)C.[NH2:4][OH:5].C[O:7][C:8](=O)[CH:9]([N:14]([CH3:39])[C:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)=[O:16])[C:10]([NH:12][CH3:13])=[O:11]>C1COCC1>[OH:5][NH:4][C:8](=[O:7])[CH:9]([N:14]([CH3:39])[C:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)=[O:16])[C:10]([NH:12][CH3:13])=[O:11]

Participants

5

Reactant 3

HCID 702EthanolHCID 787HydroxylamineHCID 712681684-{3-[(4'-{[1-Methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]propyl}morpholine

Product 1

HCID 86679255N-hydroxy-N'-methyl-2-[methyl({4'-[3-(morpholin-4-yl)propoxy]biphenyl-4-yl}carbonyl)amino]propanediamideYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethanol (1.0 mL) and a 50% aqueous solution (1.0 mL) of hydroxylamine were added to a THF (1.0 mL) solution of 4-{3-[(4′-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]propyl}morpholine (0.11 g) as obtained in Example 4-(4), and the mixture was stirred for 2 hours at room temperature. Then, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by preparative silica gel thin-layer chromatography (chloroform/methanol=90/10), and then recrystallized from ethyl acetate/hexane to obtain N-hydroxy-N′-methyl-2-[methyl({4′-[3-(morpholin-4-yl)propoxy]biphenyl-4-yl}carbonyl)amino]propanediamide (Compound 7, light brown solid) (43 mg, 39%).

Workup

  1. concentrationThen, the reaction mixture was concentrated under reduced pressure
  2. customThe resulting residue was purified by preparative silica gel thin-layer chromatography (chloroform/methanol=90/10)
  3. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-b364439ceb58472f87a0ff06ea1fe8a9
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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