Potassium Carbonate → HCID 90402783, compound

HRID 2200751Notes

Reaction equation

HRID 2200751 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)=[CH:4][CH:3]=1.Br[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 256128tert-Butyl 3-bromopropionateHCID 90403003HCID 90403003, compound2×

Product 1

HCID 90402783HCID 90402783, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

7-(4-Chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)-1H-purine-2,6(3H,7H)-dione (0.50 g, 1.07 mmol, intermediate 9), tert-butyl 3-bromopropanoate (0.22 mL, 1.29 mmol) and potassium carbonate (0.22 g, 1.61 mmol) were combined in DMF (5 mL) and heated at 100° C. for 24 h. The reaction was cooled, diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were washed with 1N lithium chloride (2×50 mL), dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to leave a white solid. This solid was purified using a 25 g silica gel flash column eluted with 10% ethyl acetate/hexanes to give tert-butyl 3-(7-(4-chlorobenzyl)-3-methyl-2,6-dioxo-8-(3-(trifluoromethoxy)phenoxy)-2,3,6,7-tetrahydro-1H-purin-1-yl)propanoate (0.26 g, 41% yield) as a white solid. LCMS retention time=4.841 min and 99% purity, LCMS MH+=595. 1H NMR (CDCl3) δ 7.12-7.46 (m, 8H), 5.41 (s, 2H), 4.29 (t, 2H, J=8 Hz), 3.53 (s, 3H), 2.61 (t, 2H, J=8 Hz), 1.43 (s, 9H).

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. washThe combined extracts were washed with 1N lithium chloride (2×50 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customto leave a white solid
  8. customThis solid was purified
  9. washeluted with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f2bf469d72cc4a2aa788ee0c48dae985
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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