Ethanol → 7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-8-phenyl-3,7-dihydro-1H-purine-2,6-dione

HRID 1727024Notes

Reaction equation

HRID 1727024 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[N:5]([CH3:23])[C:4]=2[N:3]=1.C(O)C.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[Cl-].[Li+]>C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1.[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>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[CH2:11][N:10]1[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[N:5]([CH3:23])[C:4]=2[N:3]=[C:2]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 66827Phenylboronic AcidHCID 433294Lithium ChlorideHCID 6592358-bromo-7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 117416077-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-8-phenyl-3,7-dihydro-1H-purine-2,6-dioneYield 71.2%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (100 mg, 0.25 mmol) in 260 μL aqueous sodium carbonate (2 M), 650 μL toluene, and 110 μL ethanol was treated with commercially available phenylboronic acid (34 mg, 0.27 mmol), tetrakis(triphenylphosphine)-palladium(0) (9 mg, 0.0075 mmol), and lithium chloride (catalytic). The reaction mixture was heated to 100° C. in a sealed vial and stirred overnight The reaction mixture was cooled and separated between water and ether. The aqueous layer was extracted with ether (3×) and the combined organics were dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel cartridge, Biotage, 32-63 μm, 60 Å) with 50% EtOAc:hexanes as the eluent to afford 71 mg (71% yield) of the title compound as a white solid: 1H NMR (CDCl3, 300 MHz) 7.61-7.36 (m, 5H), 7.19-7.04 (m, 2H), 6.88-6.76 (m, 1H), 5.89 (s, 2H), 3.67 (s, 3H), 3.43 (s, 3H); MS (ESP+) m/e 400 (MH+); TLC (EtOAc:hexanes/1:1) Rf=0.45.

Workup

  1. temperaturewas cooled
  2. customseparated between water and ether
  3. extractionThe aqueous layer was extracted with ether (3×)
  4. dry with materialthe combined organics were dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (silica gel cartridge, Biotage, 32-63 μm, 60 Å) with 50% EtOAc

Sources & evidence

ORD record
ord-b76f314919c841328e813a22760887b2
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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