Water → 1-[2-(2,4,5-Trifluorophenoxy)ethyl]-3-(4-isopropyl-1-piperazinyl)-2(1H)-pyrazinone

HRID 1295716Notes

Reaction equation

HRID 1295716 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[C:11](=[O:16])[NH:12][CH:13]=[CH:14][N:15]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].CC([O-])(C)C.[K+].CS(O[CH2:28][CH2:29][O:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])(=O)=O.O>C1COCC1>[F:39][C:32]1[CH:33]=[C:34]([F:38])[C:35]([F:37])=[CH:36][C:31]=1[O:30][CH2:29][CH2:28][N:12]1[CH:13]=[CH:14][N:15]=[C:10]([N:7]2[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]2)[C:11]1=[O:16]

Participants

6

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 693643353-(4-Isopropyl-1-piperazinyl)-2(1H)-pyrazinoneHCID 865916192-(2,4,5-Trifluorophenoxy)ethyl methanesulfonate

Product 1

HCID 99780381-[2-(2,4,5-Trifluorophenoxy)ethyl]-3-(4-isopropyl-1-piperazinyl)-2(1H)-pyrazinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 3-(4-isopropyl-1-piperazinyl)-2(1H)-pyrazinone (0.58 g, 2.6 mmol; from Step 2) and t-BuOK (440 mg, 3.90 mmol) in THF (40 mL) was stirred until the mixture became thick (about 10 min), and then a solution of 2-(2,4,5-trifluorophenoxy)ethyl methanesulfonate (0.90 g, 2.2 mmol; from Example 54, Step 4) in THF (10 mL) was added. After being stirred for 5 days at ambient temperature, HPLC showed only 25% conversion. The reaction solution was then heated to 60° C. overnight which gave almost full conversion. The reaction was worked up according to the following: water was added, THF was evaporated off and the aqueous mixture was extracted twice with EtOAc, dried and concentrated to yield 1.18 g of the crude product as a yellow oil. Purification by chromatography on silica gel (eluent: 2.5% MeOH in CHCl3+NH3 (g)) gave the title compound as a colourless oil, which solidified upon cooling. Yield: 120 mg (14%). HPLC purity: 99%. MS m/z 397 (M+H)+. HRMS m/z calcd for C19H23F3N4O2 (M)+ 396.1773, found 396.1771.

Workup

  1. custom(about 10 min)
  2. stirringAfter being stirred for 5 days at ambient temperature
  3. customgave almost full conversion
  4. additionwas added
  5. customTHF was evaporated off
  6. extractionthe aqueous mixture was extracted twice with EtOAc
  7. customdried
  8. concentrationconcentrated
  9. customto yield 1.18 g of the crude product as a yellow oil
  10. customPurification by chromatography on silica gel (eluent: 2.5% MeOH in CHCl3+NH3 (g))

Sources & evidence

ORD record
ord-ae6219c624e047bfa4b8cd0a285943ff
Source dataset
uspto-grants-2007_07
Patent number
US07244722B2

Reaction notes

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