Triethylamine → 1-(2,6-Difluoro-pyridin-4-ylmethyl)-6-(3,5-dimethyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione

HRID 426165Notes

Reaction equation

HRID 426165 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([F:10])[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:23][C:24]1[CH:25]=[C:26]([CH:39]=[C:40]([CH3:42])[CH:41]=1)[O:27][C:28]1[NH:33][C:32](=[O:34])[NH:31][C:30](=[O:35])[C:29]=1[CH:36]([CH3:38])[CH3:37].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:33]2[C:28]([O:27][C:26]3[CH:25]=[C:24]([CH3:23])[CH:41]=[C:40]([CH3:42])[CH:39]=3)=[C:29]([CH:36]([CH3:37])[CH3:38])[C:30](=[O:35])[NH:31][C:32]2=[O:34])[CH:5]=[C:4]([F:10])[N:3]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 222565785-Isopropyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedioneHCID 59184676(2,6-Difluoropyridin-4-yl)methanol

Product 1

HCID 667054791-(2,6-Difluoro-pyridin-4-ylmethyl)-6-(3,5-dimethyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dioneYield 50%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

(2,6-Difluoro-pyridin-4-yl)-methanol (145 mg, 1 mmol) was dissolved in chloroform (10 ml) and cooled in an ice bath under nitrogen atmosphere. With stirring, triethylamine (210 μl, 1.5 mmol) was added and methanesulfonyl chloride (90 μl, 1.2 mmol) was added dropwise. After stirring for 1.1 hr., the reaction mixture was washed with saturated aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo for ca. 20 min. and mixed with 6-(3,5-Dimethyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione (274 mg, 1 mmol), powdered anhydrous potassium carbonate (138 mg, 1 mmol), and lithium iodide (134 mg, 1 mmol). DMF (5 ml) was then added to the mixture at room temperature and stirred for ca. 4 hr. After evaporation of DMF, the residue was dissolved in methanol-chloroform (1:9) and filtered through celite pad. The filtrate was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 200 mg (50%) of a white solid. 1H-NMR (300 MHz, CDCl3) δ 1.14 (6H, d, J=6.7 Hz), 2.27 (6H, s), 2.78 (1H, m), 4.90 (2H, s), 6.44 (2H, s), 6.61 (2H, s), 6.76 (1H, s), 8.81 (1H, s); m/z (EI) 401 (M+).

Workup

  1. temperaturecooled in an ice bath under nitrogen atmosphere
  2. stirringAfter stirring for 1.1 hr
  3. wash, the reaction mixture was washed with saturated aqueous sodium bicarbonate
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was further dried in high vacuo for ca. 20 min.
  8. stirringstirred for ca. 4 hr
  9. customAfter evaporation of DMF
  10. dissolutionthe residue was dissolved in methanol-chloroform (1:9)
  11. filtrationfiltered through celite pad
  12. customThe filtrate was then evaporated in vacuo
  13. customthe residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2))

Sources & evidence

ORD record
ord-0d6b161869254923beab0ef0255b3eb1
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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