Toluene → HCID 74222634, compound

HRID 1478526Notes

Reaction equation

HRID 1478526 reaction equation
Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:10]([Cl:18])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:27]3[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=3)([C:21]3[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[OH:20])[CH:8]=2)[N:3]=1.C1(C)C=CC=CC=1.[CH3:40][O-:41].[Na+]>CCOC(C)=O>[Cl:18][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:19]([C:27]3[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=3)([C:21]3[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[OH:20])[CH:8]=2)[N:3]=[C:2]([O:41][CH3:40])[C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 10942334Sodium MethoxideHCID 118005550HCID 118005550, compound

Product 1

HCID 74222634HCID 74222634, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(2,4-Dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)pyrimidin-2-ylmethanol (156 mg, 0.337 mmol, Example 55), toluene (2 mL), and sodium methoxide (365 mg, 6.75 mmol) were combined in a round bottom flask equipped with a stirbar and condenser under an N2 atmosphere. The contents were heated to reflux and refluxed overnight. The reaction was cooled and the contents were transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl then saturated, aqueous NaHCO3 solutions. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with 0.05% trifluoroacetic acid in water as eluent. The fractions from the purification containing the desired product were transferred to a separatory funnel with EtOAc and extracted with a saturated, aqueous NaHCO3 solution. The aqueous layer was separated, extracted with EtOAc, then the combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure to provide the title compound. MS (ESI): mass calcd. for C25H20ClN5O2, 457.1; m/z found, 458.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 8.81 (d, J=4.9 Hz, 2H), 8.48 (d, J=1.8 Hz, 1H), 7.92-7.81 (m, 2H), 7.54-7.39 (m, 4H), 7.36-7.28 (m, 3H), 6.55 (s, 1H), 6.15 (s, 1H), 3.98 (s, 3H), 3.40 (s, 3H).

Workup

  1. customequipped with a stirbar and condenser under an N2 atmosphere
  2. temperatureThe contents were heated
  3. temperatureto reflux
  4. temperaturerefluxed overnight
  5. temperatureThe reaction was cooled
  6. extractionextracted with saturated, aqueous NH4Cl
  7. customThe organic phase was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified via reverse phase chromatography
  12. customThe fractions from the purification
  13. additioncontaining the desired product
  14. customwere transferred to a separatory funnel with EtOAc
  15. extractionextracted with a saturated, aqueous NaHCO3 solution
  16. customThe aqueous layer was separated
  17. extractionextracted with EtOAc
  18. dry with materialthe combined organic phases were dried over MgSO4
  19. filtrationfiltered
  20. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-af667fe065d4493595d73307aceab4c0
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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