Potassium Carbonate → 8-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione

HRID 2200629Notes

Reaction equation

HRID 2200629 reaction equation
[Br:1][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])[NH:7][C:6](=[O:20])[N:5]([CH3:21])[C:4]=2[N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][CH2:30][CH2:31][O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.O>[Br:1][C:2]1[N:10]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:29][CH2:30][CH2:31][O:32][Si:33]([C:36]([CH3:37])([CH3:39])[CH3:38])([CH3:34])[CH3:35])[C:6](=[O:20])[N:5]([CH3:21])[C:4]=2[N:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 11089258-bromo-7-(4-chlorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 904028568-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dioneYield 78%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

8-Bromo-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,71-1)-dione (33.4 g, 90.4 mmol, intermediate 8), potassium carbonate (25.0 g, 180.8 mmol) and TBAI (0.225 g) were combined in DMF (460 mL). To the mixture was added (3-bromopropoxy)(tert-butyl)dimethylsilane (25.17 g, 99.4 mmol) and the reaction was heated at 100° C. for 4 h. The reaction was cooled to room temperature, diluted with water (1.2 L) and extracted with ethyl acetate (3×400 mL). The combined organic extracts were washed with 1N lithium chloride (2×500 mL), dried with magnesium sulfate, filtered and the solvent removed under reduced pressure to give a light golden oil. The oil was purified using 2×120 g silica gel columns eluted with 10% ethyl acetate/hexanes to yield 8-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (38.3 g, 78% yield) as an off-white solid. LCMS retention time=5.083 min and 99% purity, LCMS MH+ 543. 1H NMR (CDCl3) δ 7.29-7.34 (m, 4H), 5.50 (s, 2H), 4.08 (t, 2H, J=8 Hz), 3.70 (t, 2H, J=8 Hz), 3.53 (s, 3H), 1.83-1.90 (m, 2H), 0.86(s, 9H), 0.02 (s, 6H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×400 mL)
  3. washThe combined organic extracts were washed with 1N lithium chloride (2×500 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customto give a light golden oil
  8. customThe oil was purified
  9. washeluted with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f9b05fd36d6a49aba98c5f6495ed2da1
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

Loading…