Water → 3-[(E)-{[(6-aminopyridin-2-yl)methoxy]imino}(phenyl)methyl]-4-methyl-1,2,4-oxadiazol-5(4H)-one

HRID 1528340Notes

Reaction equation

HRID 1528340 reaction equation
[C:1]([C:9]1[N:13]([CH3:14])[C:12](=[O:15])[O:11][N:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:16][O:17][CH2:18][C:19]1[N:24]=[C:23]([NH2:25])[CH:22]=[CH:21][CH:20]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CC(O)C>[NH2:25][C:23]1[N:24]=[C:19]([CH2:18][O:17]/[N:16]=[C:1](/[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)\[C:9]2[N:13]([CH3:14])[C:12](=[O:15])[O:11][N:10]=2)[CH:20]=[CH:21][CH:22]=1.[NH2:25][C:23]1[N:24]=[C:19]([CH2:18][O:17]/[N:16]=[C:1](\[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)/[C:9]2[N:13]([CH3:14])[C:12](=[O:15])[O:11][N:10]=2)[CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 450795102-Pyridinamine, 6-[(aminooxy)methyl]-HCID 894434633-benzoyl-4-methyl-1,2,4-oxadiazol-5(4H)-one

Product 2

HCID 894436403-[(Z)-{[(6-aminopyridin-2-yl)methoxy]imino}(phenyl)methyl]-4-methyl-1,2,4-oxadiazol-5(4H)-oneYield 8%HCID 894438773-[(E)-{[(6-aminopyridin-2-yl)methoxy]imino}(phenyl)methyl]-4-methyl-1,2,4-oxadiazol-5(4H)-oneYield 25%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

In a microwave tube, to a solution of 3-benzoyl-4-methyl-1,2,4-oxadiazol-5(4H)-one (500 mg, 2.44 mmol, 1 eq.) in iPrOH (10 ml) were added 6-[(aminooxy)methyl]pyridin-2-amine (340 mg, 2.44 mmol, 1 eq.) followed by pTSA.H2O (578 mg, 2.93 mmol, 1.2 eq.). The reaction was microwaved at 160° C. for 2 h then was quenched by addition of water and extracted with EtOAc (3×50 ml). The organics were combined, washed with aq. sat. NaHCO3, dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give 3-[(Z)-{[(6-aminopyridin-2-yl)methoxy]imino}(phenyl)methyl]-4-methyl-1,2,4-oxadiazol-5(4H)-one (200 mg, 25%) and 3-[(E)-{[(6-aminopyridin-2-yl)methoxy]imino}(phenyl)methyl]-4-methyl-1,2,4-oxadiazol-5(4H)-one (62 mg, 8%).

Workup

  1. customThe reaction was microwaved at 160° C. for 2 h
  2. customthen was quenched by addition of water
  3. extractionextracted with EtOAc (3×50 ml)
  4. washwashed with aq. sat. NaHCO3
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-8b022ff53db14834b8bf4f9c06e6d735
Source dataset
uspto-grants-2015_07
Patent number
US09090600B2

Reaction notes

Loading…