Water → HCID 178456684, compound

HRID 2044713Notes

Reaction equation

HRID 2044713 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[NH:15])=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])O.[K+].O.Cl[CH2:27][C:28]([C:30]1[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=1)=O>C1COCC1.[Na+].[Cl-]>[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]2[NH:16][CH:27]=[C:28]([C:30]3[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=3)[N:15]=2)=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 516893Potassium BicarbonateHCID 197001614-Benzyloxy-2-fluoro-benzamidine hydrochlorideHCID 712991852-chloro-1-(1-isopropyl-1H-1,2,4-triazol-5-yl)ethanone

Product 1

HCID 178456684HCID 178456684, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-benzyloxy-2-fluoro-benzamidine hydrochloride (74.5 g, 0.265 mol) in THF (705 mL) was treated with potassium hydrogen carbonate (106 g, 1.06 mol) and H2O (150 mL). The resultant mixture was heated to reflux to give a white suspension. Whilst maintaining gentle reflux and mechanical stirring (500 rpm) a solution of 2-chloro-1-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-ethanone (50 g, 0.265 mol) was added dropwise over 40 min. The resultant suspension gradually dissolved giving a dark red mixture that was refluxed for 18 h. The mixture was cooled to RT, diluted with saturated aqueous NaCl solution (500 mL) and extracted with EtOAc (500 mL). The organic extract was washed with saturated aqueous NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to give a pink solid The solid was triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL), collected by filtration, washed with a MTBE/pentane mixture and dried in vacuo to give 5-[2-(4-Benzyloxy-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole as a pale pink solid (84 g, 84%). 1H NMR (400 MHz, d6-DMSO): 7.95-7.93 (2H, m), 7.76 (1H, s), 7.44-7.42 (5H, m), 7.12 (1H, dd, J=13.10, 2.52 Hz), 7.03 (1H, dd, J=8.74, 2.47 Hz), 5.90 (1H, m), 5.21 (2H, s), 1.46 (6H, d, J=6.60 Hz).

Workup

  1. temperatureto reflux
  2. customto give a white suspension
  3. temperatureWhilst maintaining gentle
  4. temperaturereflux
  5. additionwas added dropwise over 40 min
  6. customgiving a dark red mixture that
  7. temperaturewas refluxed for 18 h
  8. extractionextracted with EtOAc (500 mL)
  9. extractionThe organic extract
  10. washwas washed with saturated aqueous NaCl solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a pink solid The solid
  15. customwas triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL)
  16. filtrationcollected by filtration
  17. washwashed with a MTBE/pentane mixture
  18. customdried in vacuo

Sources & evidence

ORD record
ord-2502e753ef1b44c59816b522d2833867
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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