Uracil → HCID 51035173, compound

HRID 1773141Notes

Reaction equation

HRID 1773141 reaction equation
P(Br)(Br)Br.Br[CH2:6][C:7]1[O:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])=[CH:10][CH:11]=1.[NH:21]1[CH:28]=[CH:27][C:25](=[O:26])[NH:24][C:22]1=[O:23].C(=O)([O-])[O-].[K+].[K+]>ClCCl.CN(C=O)C>[N+:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:9]1[O:8][C:7]([CH2:6][N:21]2[CH:28]=[CH:27][C:25](=[O:26])[NH:24][C:22]2=[O:23])=[CH:11][CH:10]=1)([O-:20])=[O:19]

Participants

7

Reactant 4

HCID 1174UracilHCID 11430Potassium CarbonateHCID 24614Phosphorus tribromideHCID 12631380HCID 12631380, compound

Product 1

HCID 51035173HCID 51035173, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of alcohol in dichloromethane at 0° C. was added neat PBr3 in ice bath. The solution was allowed to warm to 25° C. and then stirred for 12 h. The reaction was quenched with ice and extracted with ethyl acetate. The combined organic layers were washed with H2O, sat. NaHCO3 and brine, and dried over anhydrous Na2SO4. After the solution was filtered and concentrated under reduced pressure, the crude compound was used for the subsequent alkylation without further purification. To a solution of 2-(bromomethyl)-5-(2-nitrophenyl)furan 11a (120 mg, 0.43 mmol) and uracil (476 mg, 4.3 mmol) in anhydrous DMF (2.0 mL) was added anhydrous potassium carbonate (235 mg, 1.7 mmol) at 25° C. The resulting solution was then heated at 50° C. for 8 h. After removal of DMF under reduced pressure, the residue was diluted with CHCl3 and washed three times with water. The organic layer was dried over anhydrous MgSO4 and concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate to afford 90 mg (68%) of the uracil 13a as a white solid. 1H NMR (DMSO) δ: 11.29 (1H, s), 7.82 (1H, d, J=8.1 Hz), 7.77 (1H, d, J=7.5 Hz), 7.68 (1H, t, J=7.2 Hz), 7.60 (1H, d, J=7.8 Hz), 7.52 (1H, t, J=8.1 Hz), 6.83 (1H, d, J=3.6 Hz), 6.53 (1H, d, J=3.3 Hz), 5.57 (1H, dd, J=7.8, 1.5 Hz), 4.88 (2H, s); 13C NMR (DMSO) δ: 164.08, 151.69, 151.07, 148.39, 147.33, 145.33, 132.91, 129.70, 129.04, 124.36, 122.84, 110.38, 111.18, 102.01, 43.74.

Workup

  1. customThe reaction was quenched with ice
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with H2O, sat. NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationAfter the solution was filtered
  6. concentrationconcentrated under reduced pressure
  7. customthe crude compound was used for the subsequent alkylation without further purification
  8. temperatureThe resulting solution was then heated at 50° C. for 8 h
  9. customAfter removal of DMF under reduced pressure
  10. additionthe residue was diluted with CHCl3
  11. washwashed three times with water
  12. dry with materialThe organic layer was dried over anhydrous MgSO4
  13. concentrationconcentrated under vacuum
  14. customThe residue was purified by column chromatography
  15. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-5e7d7b87ef014b0d9952e9baeda186cd
Source dataset
uspto-grants-2016_02
Patent number
US09255088B2

Reaction notes

Loading…