Cesium carbonate → 5-Bromo-3-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-one

HRID 888432

Reaction equation

HRID 888432 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH: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])[N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:24][C:22]1[N:23]=[C:18]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH: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

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 130629693,5-Dibromo-1-methyl-1H-pyrazin-2-oneHCID 576251203-(4-Aminophenyl)-1,4-dimethylpiperazin-2-one

Product 1

HCID 576251295-Bromo-3-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-oneYield 57%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL three-neck round-bottomed flask equipped with a mechanical stirrer and reflux condenser was charged with (4) (780 mg, 3.56 mmol), 13 (998 mg, 3.73 mmol), cesium carbonate (2.36 g, 7.26 mmol) and 1,4-dioxane (40 mL). After bubbling nitrogen through the resulting solution for 30 minutes, Xantphos (0.162 g, 0.281 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.15 g, 0.165 mmol) were added, and the reaction mixture was heated at reflux for 16 h. After this time the reaction was cooled to room temperature and concentrated under reduced pressure. The resulting residue was absorbed onto silica gel and purified by flash chromatography to afford a 57% yield (818 mg) of 14 as an orange solid: mp 206-207° C.; 1H NMR (500 MHz, CDCl3) δ 8.27 (bs, 1H), 7.72 (dd, 1H, J=2.0, 8.5 Hz), 7.36 (dd, 2H, J=2.0, 8.5 Hz), 6.73 (s, 1H), 3.71 (m, 1H), 3.69 (s, 1H), 3.52 (s, 3H), 3.21 (m, 1H), 3.01 (m, 1H), 2.97 (s, 3H), 2.67 (m, 1H), 2.19 (s, 3H); MS (ESI+) m/z 406 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a mechanical stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting solution for 30 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 16 h
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was absorbed onto silica gel
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-ea56abd5a71240769d602a68816cda5b
Source dataset
uspto-grants-2012_08
Patent number
US08247550B2

Linked notes

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