Potassium Carbonate → 3-chloro-4-((2,4-difluoro-3-methylbenzyl)oxy)-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5',6-dimethyl-2H-[1,4'-bipyridin]-2-one

HRID 2199523Notes

Reaction equation

HRID 2199523 reaction equation
[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]([OH:26])([CH3:25])[CH3:24])[N:18]=3)[CH:11]=2)[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([CH3:37])[C:31]=1[F:38].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C.CCCCCCC>CN(C)C=O.C1OCCOCCOCCOCCOCCOC1>[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[C:12]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]([OH:26])([CH3:24])[CH3:25])[N:18]=3)[CH:11]=2)[C:5]([CH3:9])=[CH:6][C:7]=1[O:8][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([CH3:37])[C:31]=1[F:38]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 21899848Ethylacetate heptaneHCID 866993063-chloro-4-hydroxy-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5',6-dimethyl-2H-[1,4'-bipyridin]-2-oneHCID 866993081-(Bromomethyl)-2,4-difluoro-3-methylbenzene

Product 1

HCID 717690183-chloro-4-((2,4-difluoro-3-methylbenzyl)oxy)-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5',6-dimethyl-2H-[1,4'-bipyridin]-2-oneYield 60.5%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chloro-4-hydroxy-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-2H-[1,4′-bipyridin]-2-one (386 mg, 1.0 mmol) in N,N-dimethylformamide (1.7 mL) was added 1-(bromomethyl)-2,4-difluoro-3-methylbenzene (243 mg, 1.1 mmol), potassium carbonate (0.35 g, 2.52 mmol) and 18-crown-6 (7 mg). The slurry was stirred at ambient temperature for 18 hours. The reaction was partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The solution was concentrated in vacuo to provide a brown oil. Normal phase chromatography (ethyl acetate/heptane) provided 319 mg of the alkylated product: MS (M+H) 528.

Workup

  1. customThe reaction was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationThe solution was concentrated in vacuo
  5. customto provide a brown oil

Sources & evidence

ORD record
ord-f8d983b88d9241aca12e35df189b8673
Source dataset
uspto-grants-2016_06
Patent number
US09359300B2

Reaction notes

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