Cesium carbonate → 5-Bromo-3-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 519310Notes

Reaction equation

HRID 519310 reaction equation
[F:1][CH2:2][CH:3]1[CH2:8][N:7]([C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-])=O)=[CH:13][CH:14]=2)[CH2:6][CH2:5][N:4]1[CH3:18].Br[C:20]1[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=[C:24]([Br:26])[CH:25]=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:26][C:24]1[CH:25]=[C:20]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([N:7]3[CH2:6][CH2:5][N:4]([CH3:18])[CH:3]([CH2:2][F:1])[CH2:8]3)=[CH:10][N:11]=2)[C:21](=[O:28])[N:22]([CH3:27])[CH:23]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 580437532-(Fluoromethyl)-1-methyl-4-(6-nitropyridin-3-yl)piperazine

Product 1

HCID 580437315-Bromo-3-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-oneYield 53.6%

Reagents, catalysts & solvents 2

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

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 111e (crude, 14.1 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (4.5 g, 16.9 mmol) and cesium carbonate (11.5 g, 35.2 mmol). After bubbling nitrogen through the resulting solution for 30 min, Xantphos (820 mg, 1.41 mmol) and tris(dibenzylideneacetone)dipalladium(0) (645 mg, 0.7 mmol) were added, and the reaction mixture was heated at reflux for 15 h. After this time the reaction was cooled to room temperature, filtered and concentrated to afford a black solid as the crude product. Then it was purified on silica gel (DCM:MeOH=100:1 to 50:1) to afford 111g as a yellow solid (3.1 g, yield 50%).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting solution for 30 min
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 15 h
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a black solid as the crude product
  9. customThen it was purified on silica gel (DCM:MeOH=100:1 to 50:1)

Sources & evidence

ORD record
ord-49f3f0dd43b842bca0ae8cfeae810c20
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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