Diisopropylethylamine → (R)-5-bromo-3-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-one

HRID 1411517Notes

Reaction equation

HRID 1411517 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[N:13]([CH3:14])[CH2:12][CH2:11][N:10]([CH3:15])[C:9]2=[O:16])=[CH:4][CH:3]=1.Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])C=1.C([N:30](C(C)C)CC)(C)C>CC(O)C>[Br:24][C:22]1[N:30]=[C:18]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C@@H:8]3[C:9](=[O:16])[N:10]([CH3:15])[CH2:11][CH2:12][N:13]3[CH3:14])=[CH:6][CH:7]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 86684196(R)-3-(4-aminophenyl)-1,4-dimethylpiperazin-2-one

Product 1

HCID 57625140(R)-5-bromo-3-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-oneYield 90%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube equipped with a magnetic stirrer was charged with (R)-3-(4-aminophenyl)-1,4-dimethylpiperazin-2-one (1.08 g, 5 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.47 g, 5.5 mmol), diisopropylethylamine (1.94 g, 15 mmol), and iPrOH (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. overnight. After cooling down to room temperature, water (20 mL) was added to, and the mixture was extracted with ethyl acetate (50 mL×2). The organic layer was separated, combined, dried over anhydrous sodium sulfate, and concentrated. The resulting residue was purified by silica gel column chromatography eluting with dichloromethane/methanol (10:1, UV) to afford 114a (1.8 g, 90%) as a red solid. LCMS: [M+H]+ 406

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureAfter cooling down to room temperature
  4. additionwater (20 mL) was added to, and the mixture
  5. extractionwas extracted with ethyl acetate (50 mL×2)
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe resulting residue was purified by silica gel column chromatography
  10. washeluting with dichloromethane/methanol (10:1, UV)

Sources & evidence

ORD record
ord-c4a0eafbb18147a4aacf08dc5f007713
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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