Caffeine → 8-(4-chlorophenyl)-1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione

HRID 522506

Reaction equation

HRID 522506 reaction equation
[Li+].[Cl-].[CH3:3][N:4]1[C:12](=[O:13])[C:11]2[N:10]([CH3:14])[CH:9]=[N:8][C:7]=2[N:6]([CH3:15])[C:5]1=[O:16].[Cl:17][C:18]1[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:9]2[N:10]([CH3:14])[C:11]3[C:12](=[O:13])[N:4]([CH3:3])[C:5](=[O:16])[N:6]([CH3:15])[C:7]=3[N:8]=2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 2519CaffeineHCID 125101-Chloro-4-iodobenzeneHCID 433294Lithium Chloride

Product 1

HCID 238532358-(4-chlorophenyl)-1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dioneYield 74.2%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

TMPZnCl.LiCl (2) (1.3 M in THF, 0.85 mL, 1.1 mmol) was added to a solution of 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione (12) (194 mg, 1.0 mmol) in THF (2 mL) at 25° C. and the reaction mixture was then stirred at this temperature for max. 5 min. Pd(dba)2 (17 mg, 3 mol %) and P(o-furyl)3 (14 mg, 6 mol %) dissolved in THF (2 mL), and mixed with 1-chloro-4-iodobenzene (310 mg, 1.3 mmol, 1.3 equiv) were then transferred via cannula to the reaction mixture. The resulting mixture was stirred for 1 h at 25° C. The reaction mixture was then quenched with a sat. aq. NH4Cl solution (20 mL), extracted with diethyl ether (3×50 mL) and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. Purification by flash-chromatography (CH2Cl2/ether, 1:1) furnished compound 14a (226 mg, 74%) as a colourless solid.

Workup

  1. custom5 min
  2. stirringThe resulting mixture was stirred for 1 h at 25° C
  3. customThe reaction mixture was then quenched with a sat. aq. NH4Cl solution (20 mL)
  4. extractionextracted with diethyl ether (3×50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationAfter filtration
  7. customthe solvent was evaporated in vacuo
  8. customPurification by flash-chromatography (CH2Cl2/ether, 1:1)

Sources & evidence

ORD record
ord-45bc23b5626d4cf4851f9d8b595472be
Source dataset
uspto-grants-2016_05
Patent number
US09334237B2

Linked notes

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