Toluene → HCID 90402782, compound

HRID 2200756Notes

Reaction equation

HRID 2200756 reaction equation
[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C:13](=[O:29])[N:12]([CH3:30])[C:11]=2[N:10]=[C:9]1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[Cl:45].C1(C)C=CC=CC=1>C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[N:14]([CH2:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C:13](=[O:29])[N:12]([CH3:30])[C:11]=2[N:10]=[C:9]1[C:42]1[CH:41]=[CH:40][C:39]([Cl:38])=[C:44]([Cl:45])[CH:43]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 90402849HCID 90402849, compound2×

Product 1

HCID 90402782HCID 90402782, compoundYield 86.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

Step 1 7-Benzyl-8-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.50 g, 0.985 mmol, intermediate 83), potassium carbonate (0.326 g, 2.36 mmol), tetrakis(triphenylphosphine) palladium(0) (0.032 g, 0.028 mmol) and 3,4-dichlorophenyl boronic acid (0.206 g, 1.08 mmol) were combined in ethanol (12.0 mL), toluene (2.0 mL) and water (2.0 mL) in a sealed vial. The reaction was heated at 85° C. for 18 h. The reaction was cooled and filtered through Celite. The filtrate was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to yield a golden solid. The solid was purified using a 25 g silica gel CombiFlash column eluted with 20% ethyl acetate/hexanes to give 7-benzyl-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-8-(3,4-dichlorophenyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.49 g, 86% yield) as a golden oil. LCMS retention time=5.489 min and 97% purity, LCMS MH+=573.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through Celite
  3. additionThe filtrate was diluted with water (100 mL)
  4. extractionextracted with ethyl acetate (3×75 mL)
  5. dry with materialThe combined extracts were dried with magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto yield a golden solid
  9. customThe solid was purified
  10. washeluted with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-439f0f95186e41c487167dc618441680
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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