HCID 178491480, compound → Nvs-crf38

HRID 1696867Notes

Reaction equation

HRID 1696867 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[C:12]([CH3:13])=[N:11][NH:10][C:9]=2[O:14][CH:15]([CH3:27])[C:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[CH3:26])=O)[N:3]=1>ClCCCl.CCOCC.CCCC(C)C.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[C:12]([CH3:13])=[N:11][N:10]3[C:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=4[CH3:26])=[C:15]([CH3:27])[O:14][C:9]=23)[N:3]=1

Participants

5

Reactant 1

HCID 178491480HCID 178491480, compound

Product 1

HCID 44816934Nvs-crf38

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 111,2-DichloroethaneSolventHCID 21882825Ether isohexaneSolvent

Conditions

Temperature
85 °C

Procedure

To a dispersion of 2-[4-(3,5-dimethyl-[1,2,4]triazol-1-yl)-5-methyl-2H-pyrazol-3-yloxy]-1-(4-methoxy-2-methyl-phenyl)-propan-1-one (step 1) (0.905 g, 2.45 mmol) in 1,2-dichloroethane (20 ml) was added titanium tetrachloride (0.675 ml, 6.12 mmol). The reaction mixture was heated to 85° C. for 2.5 hours and left at RT overnight. The mixture was quenched carefully with sat. NH4Cl (50 ml) and extracted with EtOAc (2×50 ml). The combined organic extracts were washed with NaHCO3 (50 ml), brine, dried (MgSO4) and concentrated in vacuo to afford a dark brown oil. The crude oil was then taken up in 10% Et2O/iso-hexane (50 ml) and the brown solution was sonicated. The resulting solid was collected and washed with iso-hexane to give a cream coloured solid. Purification of this solid by recrystallisation from hot Et2O (˜40 ml) yielded the title compound as tan crystals; LC-MS Rt 3.7 mins; MS m/z 352.1 [M+H]+; Method=10minLC_v001.

Workup

  1. customThe mixture was quenched carefully with sat. NH4Cl (50 ml)
  2. extractionextracted with EtOAc (2×50 ml)
  3. washThe combined organic extracts were washed with NaHCO3 (50 ml), brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto afford a dark brown oil
  7. customthe brown solution was sonicated
  8. customThe resulting solid was collected
  9. washwashed with iso-hexane
  10. customto give a cream
  11. customPurification of this solid
  12. customby recrystallisation from hot Et2O (˜40 ml)

Sources & evidence

ORD record
ord-9e7fe51bf05a44a89d7aa8bdfd938f66
Source dataset
uspto-grants-2012_04
Patent number
US08163785B2

Reaction notes

Loading…