Ethanol → HCID 178433220, compound

HRID 241458Notes

Reaction equation

HRID 241458 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[N:9]=CC=C[N:5]2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1.C[CH2:22][OH:23].[OH2:24].NN>>[CH:22]([O-:23])=[O:24].[CH3:1][C:2]1[N:3]=[C:4]([NH3+:9])[NH:5][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 24654Hydrazine hydrate (1:1)HCID 710597752-Methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine

Product 1

HCID 178433220HCID 178433220, compoundYield 72.9%

Conditions

Temperature
125 °C

Procedure

Suspend 2-methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine (2.176 g, 7.849 mmol) in EtOH (15.00 mL, 257.646 mmol). Add hydrazine hydrate (4.00 mL, 81.821 mmol). Heat to 125° C. with microwave irradiation. Stir for 30 minutes, and concentrate under reduced pressure. Dissolve the residue in EtOAc (75 mL); wash the organic extracts with water (3×50 mL); and then wash with a saturated NaCl aqueous solution (50 mL). Dry the organic extracts over Na2SO4; filter; collect the filtrate; and concentrate the filtrate in vacuo. Purify by reverse phase flash chromatography (Analogix® 150 g @ 40 mL/min) eluting with a gradient of 5-30% ACN/water over 35 minutes. Material precipitates upon loading samplet. Collect the resulting white material from the samplet and reflux it MeOH for 15 minutes. Filter the MeOH mixture through diatomaceous earth collect the filtrate, and wash the diatomaceous earth with MeOH. Concentrate the combined filtrates under reduced pressure to give the title compound (1.643 g, 72.9% yield) as a white crystalline solid. 1H NMR (400.43 MHz, d6-DMSO) δ 13.14-13.11 (m, 2H), 7.77 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.2 Hz, 2H), 7.47 (s, 2H), 2.26 (s, 3H). ES/MS (m/z) 241.99 (parent+1, formate not detected).

Workup

  1. concentrationconcentrate under reduced pressure
  2. dissolutionDissolve the residue in EtOAc (75 mL)
  3. washwash the organic extracts with water (3×50 mL)
  4. washand then wash with a saturated NaCl aqueous solution (50 mL)
  5. dry with materialDry the organic extracts over Na2SO4
  6. filtrationfilter
  7. customcollect the filtrate
  8. concentrationand concentrate the filtrate in vacuo
  9. customPurify by reverse phase flash chromatography (Analogix® 150 g @ 40 mL/min)
  10. washeluting with a gradient of 5-30% ACN/water over 35 minutes
  11. customMaterial precipitates
  12. customCollect the resulting white material from the samplet
  13. temperaturereflux it MeOH for 15 minutes
  14. filtrationFilter the MeOH mixture through diatomaceous earth
  15. customcollect the filtrate
  16. washwash the diatomaceous earth with MeOH
  17. concentrationConcentrate the combined filtrates under reduced pressure

Sources & evidence

ORD record
ord-0eb7948292e446a3be074faba2564161
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

Loading…