Potassium Carbonate → 3-ethyl-1-(3-hydroxypropyl)-7-((6-methylpyridin-3-yl)methyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200687Notes

Reaction equation

HRID 2200687 reaction equation
[CH2:1]([N:3]1[C:11]2[N:10]=[C:9]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=3)[NH:8][C:7]=2[C:6](=[O:24])[N:5]([CH2:25][CH2:26][CH2:27][OH:28])[C:4]1=[O:29])[CH3:2].Cl[CH2:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:38])=[N:36][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH2:1]([N:3]1[C:11]2[N:10]=[C:9]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:22])([F:23])[F:21])[CH:14]=3)[N:8]([CH2:31][C:32]3[CH:37]=[N:36][C:35]([CH3:38])=[CH:34][CH:33]=3)[C:7]=2[C:6](=[O:24])[N:5]([CH2:25][CH2:26][CH2:27][OH:28])[C:4]1=[O:29])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 122143385-(Chloromethyl)-2-methylpyridineHCID 904027233-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

Product 1

HCID 904024753-ethyl-1-(3-hydroxypropyl)-7-((6-methylpyridin-3-yl)methyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dioneYield 44.8%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-ethyl-1-(3-hydroxypropyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (110 mg, 0.22 mmol) in DMF (3 mL) was added 5-(chloromethyl)-2-methylpyridine (50 mg, 0.4 mmol), potassium carbonate (91 mg, 0.66 mmol), and TBAI (2 mg, 0.02 mmol). The reaction was heated at 50° C. overnight. The mixture was cooled and partitioned between ethyl acetate and water. The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a crude product, which was purified by preparative HPLC to give 3-ethyl-1-(3-hydroxypropyl)-7-((6-methylpyridin-3-yl)methyl)-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (30 mg, 44.8% yield) as a white solid.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product, which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-07fbdbbde0bb42cfa69405fa25642e4a
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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