HCID 178491480, compound → Nvs-crf38

HRID 1671309Notes

Reaction equation

HRID 1671309 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 (0.905 g, 2.45 mmol) in 1,2-dichloroethane (20 ml) is added titanium tetrachloride (0.675 ml, 6.12 mmol). The reaction mixture is heated to 85° C. for 2.5 hours and then left at RT overnight. The mixture is quenched carefully with sat. NH4Cl (50 ml) and extracted with EtOAc (2×50 ml). The combined organic extracts are washed with NaHCO3 (50 ml), brine, dried over MgSO4 and concentrated in vacuo to afford a dark brown oil. The crude oil is then taken up in 10% Et2O/iso-hexane (50 ml) and the brown solution is sonicated: no precipitation occurred immediately, but after 2 hours large crystals form. The solid is collected and washed with iso-hexane to give a cream coloured solid. Purification of this solid by recrystallisation from hot Et2O (˜40 ml) yields the title compound as tan crystals; MS: m/z=352.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 7.39 (1H, d), 7.01 (1H, d), 6.94 (1H, dd), 3.83 (3H, s), 2.30 (6H, s), 2.26 (6H, s), 2.11 (3H, s).

Workup

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

Sources & evidence

ORD record
ord-c6b1f1dea31947bfb0dc6ee50d20d0d4
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

Loading…