Dimethylformamide → 4-(2,3-Dimethyl-4-nitrophenoxy)pyridin-2-amine

HRID 2069133Notes

Reaction equation

HRID 2069133 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][N:3]=1.C1CCN2C(=NCCC2)CC1.F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[C:23]([CH3:30])[C:22]=1[CH3:31].CN(C=O)C>CC#N>[CH3:31][C:22]1[C:23]([CH3:30])=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=[CH:26][C:21]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 247212012,3-Dimethyl-4-fluoronitrobenzeneHCID 178507942HCID 178507942, compound

Product 1

HCID 585648204-(2,3-Dimethyl-4-nitrophenoxy)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a suspension of 2-aminopyridin-4-ol (339 mg, 3.07 mmol) in MeCN (4.0 mL) at RT was added DBU (570 μL, 3.78 mmol) and after 30 min a solution of 1-fluoro-2,3-dimethyl-4-nitrobenzene (400 mg, 2.36 mmol) in MeCN (2.0 mL) was added dropwise. The reaction mixture was maintained at RT for 16 hr; DMF (2.0 mL) was added and the mixture heated to 80° C. for 72 hr and then cooled to RT for 64 hr. The resulting mixture was evaporated in vacuo and the residue was partitioned between DCM (50 mL) and brine (30 mL). The organic layer was separated and dried (MgSO4) and was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 20-100%, gradient elution and then SiO2, 12 g, 50% EtOAc in isohexane, isocratic elution) to afford 4-(2,3-dimethyl-4-nitrophenoxy)pyridin-2-amine, as a yellow solid (117 mg, 19%); Rt 1.47 min (Method 2); m/z 260 (M+H)+ (ES+).

Workup

  1. temperaturethe mixture heated to 80° C. for 72 hr
  2. temperaturecooled to RT for 64 hr
  3. customThe resulting mixture was evaporated in vacuo
  4. customthe residue was partitioned between DCM (50 mL) and brine (30 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customwas evaporated in vacuo
  8. customThe residue was purified by flash column chromatography (
  9. washSiO2, 40 g, EtOAc in isohexane, 20-100%, gradient elution
  10. washSiO2, 12 g, 50% EtOAc in isohexane, isocratic elution)

Sources & evidence

ORD record
ord-0d170b5b2d834450b8c645e0a793e73c
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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