Potassium Carbonate → 6-Bromo-9-[(4-methoxyphenyl)methyl]purine

HRID 1042263Notes

Reaction equation

HRID 1042263 reaction equation
[Br:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.C(=O)([O-])[O-].[K+].[K+].[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][CH:20]=1>CN(C=O)C>[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][N:6]2[CH:5]=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[Br:1])=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 178419477HCID 178419477, compound

Product 1

HCID 596273846-Bromo-9-[(4-methoxyphenyl)methyl]purineYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

A suspension of 6-bromo-9H-purine (4.3 g, 22 mmol) in anhydrous DMF (40 mL) was treated with potassium carbonate (9.0 g, 65 mmol) and stirred for 20 min at room temperature (22° C.). The mixture was treated with 4-methoxybenzyl chloride (5.9 mL, 43 mmol) and allowed to stir for 20 h at 45° C. The solids were removed by suction filtration and the solvent removed in vacuo. The resulting crude oil was partitioned between water and 3:1 CHCl3:IPA (100 mL each). The aqueous layer was extracted with 3:1 CHCl3:IPA (100 mL). The combined organic extract was washed with saturated NaCl (70 mL), dried over Na2SO4, filtered, and concentrated in vacuo to a viscous oil. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (330 g), eluting with a gradient of 40% to 70% EtOAc in hexane, to provide 9-(4-methoxybenzyl)-6-bromo-9H-purine (2.7 g, 39% yield) as a white waxy solid; 1H NMR (400 MHz, DMSO-d6) □ ppm 3.71 (s, 3H), 5.44 (d, J=4.02 Hz, 2H), 6.90 (d, J=8.03 Hz, 2H), 7.34 (d, J=8.53 Hz, 2H), 8.76 (d, J=22.59 Hz, 1H), 8.81 (s, 1H).

Workup

  1. stirringto stir for 20 h at 45° C
  2. customThe solids were removed by suction filtration
  3. customthe solvent removed in vacuo
  4. customThe resulting crude oil was partitioned between water and 3:1 CHCl3
  5. extractionThe aqueous layer was extracted with 3:1 CHCl3
  6. extractionThe combined organic extract
  7. washwas washed with saturated NaCl (70 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a viscous oil
  11. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (330 g)
  12. washeluting with a gradient of 40% to 70% EtOAc in hexane

Sources & evidence

ORD record
ord-fa8376ee70484043b854b0877e1ba071
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

Loading…