Potassium Carbonate → 6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1-pyridin-4-ylmethyl-1H-pyrimidine-2,4-dione

HRID 426217Notes

Reaction equation

HRID 426217 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[O:9][C:10]1[NH:15][C:14](=[O:16])[NH:13][C:12](=[O:17])[C:11]=1[CH:18]([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.[I-].[Li+]>CN(C=O)C>[O:3]1[CH2:4][CH2:5][O:1][CH:2]1[C:6]1[CH:7]=[C:8]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[O:9][C:10]1[N:15]([CH2:33][C:34]2[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=2)[C:14](=[O:16])[NH:13][C:12](=[O:17])[C:11]=1[CH:18]([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 591846836-(3-[1,3]Dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione

Product 1

HCID 591847936-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1-pyridin-4-ylmethyl-1H-pyrimidine-2,4-dioneYield 40.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(3-[1,3]Dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione (2.66 g, 8 mmol) and anhydrous powdered potassium carbonate (1.31 g, 16 mmol) were dissolved in DMF (40 ml). With vigorous stirring, 4-chloromethylpyridine hydrochloride (2.21 g, 16 mmol) and lithium iodide (1 g, 8 mmol) were added in this order. The mixture was stirred for overnight at room temperature and evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through a celite pad, and the filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA:hexane (9:1)) to afford 1.36 g (40%) of 6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1-pyridin-4-ylmethyl-1H-pyrimidine-2,4-dione as a white foam. 1H NMR (200 MHz, CDCl3) δ 1.13 (6H, d, J=7.0 Hz), 2.32 (3H, s), 2.74 (1H, m), 3.98-4.17 (4H, m), 4.87 (2H, s), 5.71 (1H, s), 6.63 (1H, s), 6.79 (1H, s), 7.05 (1H, s), 7.08 (1H, s), 7.11 (1H, s), 7.53 (2H, dd, J=1.6 Hz, J=4.4 Hz), 9.37 (1H, s).

Workup

  1. customevaporated in vacuo
  2. dissolutionThe residue was dissolved in methanol-dichloromethane (1:9)
  3. filtrationfiltered through a celite pad
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was purified by silica gel column chromatography (eluent, EA:hexane (9:1))

Sources & evidence

ORD record
ord-ae76108c29b340169f7767d038c4e106
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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