Potassium Carbonate → HCID 90403025, compound

HRID 2200714Notes

Reaction equation

HRID 2200714 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][OH:23])[C:6](=[O:24])[N:5]([CH3:25])[C:4]=2[N:3]=1.[Cl:26][C:27]1[CH:28]=[C:29]([OH:38])[CH:30]=[C:31]([O:33][C:34]([F:37])([F:36])[F:35])[CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:26][C:27]1[CH:28]=[C:29]([CH:30]=[C:31]([O:33][C:34]([F:35])([F:36])[F:37])[CH:32]=1)[O:38][C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][OH:23])[C:6](=[O:24])[N:5]([CH3:25])[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 467376533-Chloro-5-(trifluoromethoxy)phenolHCID 904024691628285-95-92×

Product 1

HCID 90403025HCID 90403025, compoundYield 53.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of the 8-bromo-7-(4-chlorobenzyl)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)— dione (50 mg, 0.116 mmol, intermediate 63) in DMF (2 mL) was added 3-chloro-5-(trifluoromethoxy)phenol (29.82 mg, 0.140 mmol) followed by potassium carbonate (24.24 mg, 0.175 mmol). The reaction was stirred at 85° C. for 2 h. The reaction was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give crude product, which was purified by preparative HPLC to give 8-(3-chloro-5-(trifluoromethoxy)phenoxy)-7-(4-chlorobenzyl)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (35 mg, 53.5% yield) as white solid. 1H-NMR (CD3OD) δ 7.458-7.435(m,3H), 7.381-7.365(m,3H), 7.361(s,1H), 5.507(s,2H), 4.138-4.102(t,2H), 3.640-3.608(t,2H), 3.448(s,3H), 1.905-1.871(m,2H). LCMS retention time 3.325 min; LCMS MH+ 559.

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude product, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-1c8da4d3d90f449abcb309e3d1c7677b
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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