Cesium carbonate → 5-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-2(1H)-one

HRID 1918813Notes

Reaction equation

HRID 1918813 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([Br:15])[CH:14]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl.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]>[Br:15][C:13]1[CH:14]=[C:9]([NH:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][N:3]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 689584-AminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-one

Product 1

HCID 580440945-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-2(1H)-oneYield 49.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of pyrimidin-4-amine (2.0 g, 21 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (6.2 g, 23.1 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.96 g, 1.1 mmol), Xantphos (1.03 g, 1.79 mmol), and cesium carbonate (7.5 g, 23 mmol) in dioxane (25 mL) was heated in a sealed tube at 130° C. for 18 hours. The mixture was diluted with CH2Cl2 (100 mL) and filtered through a plug of celite. The solution was concentrated in vacuo on the rotary evaporator. The material was then dissolved in minimal CH2Cl2 (5 mL) and was triturated with Et2O (80 mL). The product was then filtered and washed with Et2O (100 mL) to afford 2.9 g (49%) of 109b.

Workup

  1. filtrationfiltered through a plug of celite
  2. concentrationThe solution was concentrated in vacuo on the rotary evaporator
  3. dissolutionThe material was then dissolved in minimal CH2Cl2 (5 mL)
  4. customwas triturated with Et2O (80 mL)
  5. filtrationThe product was then filtered
  6. washwashed with Et2O (100 mL)

Sources & evidence

ORD record
ord-d62f4ccc062d4593b84cd6475b162639
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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