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

HRID 1295713Notes

Reaction equation

HRID 1295713 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:9](=[O:14])[NH:10][CH:11]=[CH:12][N:13]=2)[CH2:4][CH2:3]1.CC([O-])(C)C.[K+].CS(O[CH2:26][CH2:27][O:28][C:29]1[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=1[F:37])(=O)=O.O>C1COCC1>[F:37][C:30]1[CH:31]=[C:32]([F:36])[C:33]([F:35])=[CH:34][C:29]=1[O:28][CH2:27][CH2:26][N:10]1[CH:11]=[CH:12][N:13]=[C:8]([N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[C:9]1=[O:14]

Participants

6

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 693657953-(4-Methyl-1-piperazinyl)-2(1H)-pyrazinoneHCID 865916192-(2,4,5-Trifluorophenoxy)ethyl methanesulfonate

Product 1

HCID 104067051-[2-(2,4,5-Trifluorophenoxy)ethyl]-3-(4-methyl-1-piperazinyl)-2(1H)-pyrazinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 3-(4-methyl-1-piperazinyl)-2(1H)-pyrazinone (obtained in Step 2 above; 0.5 g, 2.6 mmol) 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 Step 4) in THF (10 mL) was added. After being stirred for 5 days at ambient temp, HPLC showed only 50% 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 (Na2SO4) and concentrated to yield 1.08 g of the crude product as a yellow oil. Purification by chromatography on silica gel [eluent: 2% MeOH in CHCl3+NH3 (g)] gave the title compound as a yellow oil, which solidified upon cooling. Yield: 304 mg (32%). HPLC purity: 100%. MS m/z 369 (M+H)+. HRMS m/z calcd for C17H19F3N4O2 (M)+ 368.1460, found 368.1462.

Workup

  1. custom(about 10 min)
  2. stirringAfter being stirred for 5 days at ambient temp
  3. customgave almost full conversion
  4. additionwas added
  5. customTHF was evaporated off
  6. extractionthe aqueous mixture was extracted twice with EtOAc
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customto yield 1.08 g of the crude product as a yellow oil
  10. customPurification by chromatography on silica gel [eluent: 2% MeOH in CHCl3+NH3 (g)]

Sources & evidence

ORD record
ord-42fbfcdb05d34260a52d3247dfc464f2
Source dataset
uspto-grants-2007_07
Patent number
US07244722B2

Reaction notes

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