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

HRID 2199524Notes

Reaction equation

HRID 2199524 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:31]=[N:32][CH:33]=[C:34]([CH3:36])[CH:35]=1.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:31]=[N:32][CH:33]=[C:34]([CH3:36])[CH:35]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 119627433-(Bromomethyl)-5-methylpyridineHCID 21899848Ethylacetate heptaneHCID 866993063-chloro-4-hydroxy-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5',6-dimethyl-2H-[1,4'-bipyridin]-2-one

Product 1

HCID 717685993-chloro-2'-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5',6-dimethyl-4-((5-methylpyridin-3-yl)methoxy)-2H-[1,4'-bipyridin]-2-oneYield 71.3%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6228DimethylformamideSolvent

Procedure

To the intermediate at Step F, 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 3-(bromomethyl)-5-methylpyridine (205 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 351 mg of the alkylated product MS (M+H) 493.

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-6fe85a1a8d9b460eb1605241bb1d8de0
Source dataset
uspto-grants-2016_06
Patent number
US09359300B2

Reaction notes

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