Sodium Carbonate → 2-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purine

HRID 522281Notes

Reaction equation

HRID 522281 reaction equation
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[C:27]([C:41]([F:44])([F:43])[F:42])[CH:26]=1.[Cl:45][C:46]1[N:54]=[C:53]2[C:49]([N:50]=[CH:51][N:52]2[CH3:55])=[C:48](Cl)[N:47]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O.O>[Cl:45][C:46]1[N:54]=[C:53]2[C:49]([N:50]=[CH:51][N:52]2[CH3:55])=[C:48]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)=[C:27]([C:41]([F:44])([F:43])[F:42])[CH:26]=2)[N:47]=1

Participants

11

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 17125532,6-dichloro-9-methyl-9H-purineHCID 2733548Bis(pinacolato)diboraneHCID 900657114-Bromo-1-[(4-methoxybenzyl)oxy]-2-(trifluoromethyl)benzene

Product 1

HCID 1178996942-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purineYield 16.6%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Bis(pinacolato)diboron (4.12 g), potassium acetate (4.35 g), and dichlorobis(triphenylphosphine)palladium (II) (1.04 g) were added to a solution of 4-bromo-1-[(4-methoxybenzyl)oxy]-2-(trifluoromethyl)benzene (5.87 g) in dioxane (90 mL) at room temperature in an argon atmosphere, and the mixture was stirred at 100° C. for 2 hours. After the reaction mixture was cooled to room temperature, 2,6-dichloro-9-methyl-9H-purine (3 g), Na2CO3 (4.7 g), tetrakis(triphenylphosphine)palladium (0) (854 mg), and water (15 mL) were added thereto. The reaction mixture was stirred at 100° C. for 4 hours. After the reaction mixture was cooled to room temperature, EtOAc was added thereto, followed by stirring, and the insoluble material was separated by filtration using Celite. Extraction was performed on the filtrate using EtOAc, and the extract was washed with water. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=4:1 to 1:1), whereby 2-chloro-6-{4-[(4-methoxybenzyl)oxy]-3-(trifluoromethyl)phenyl}-9-methyl-9H-purine (1.1 g) was obtained as a white solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringThe reaction mixture was stirred at 100° C. for 4 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. stirringby stirring
  5. customthe insoluble material was separated by filtration
  6. extractionExtraction
  7. washthe extract was washed with water
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=4:1 to 1:1)

Sources & evidence

ORD record
ord-40b906f201ca4b50b130da7cb23af559
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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