Iodoethane → HCID 59299529, compound

HRID 1943823Notes

Reaction equation

HRID 1943823 reaction equation
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][C:17]([F:20])([F:19])[F:18])[C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:28][CH3:29].N1CCOCC1>CN(C=O)C.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>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH2:28][CH3:29])[C:6](=[O:15])[N:5]([CH2:16][C:17]([F:18])([F:19])[F:20])[C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 6340IodoethaneHCID 8083MorpholineHCID 10796Cesium carbonateHCID 59299596HCID 59299596, compound

Product 1

HCID 59299529HCID 59299529, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-chloro-7-(2-propen-1-yl)-3-(2,2,2-trifluoroethyl)-3,7-dihydro-1H-purine-2,6-dione (0.070 g, 0.23 mmol) in anhydrous DMF (2 ml) was added caesium carbonate (0.085 g, 0.26 mmol) followed by 1-iodoethane (0.061 g, 0.39 mmol). The mixture was heated for 5 h at 80° C. then stirred for 16 h at ambient temperature under an atmosphere of nitrogen. The solvent was removed under reduced pressure using a vacuum centrifuge and the residue dissolved in anhydrous THF (2.5 ml). To the mixture was added palladium tetrakis (0.030 g, 0.026 mmol) and morpholine (0.040 g, 0.45 mmol) and the reaction mixture degassed using nitrogen then stirred at ambient temperature for 72 h. The mixture was partitioned between chloroform and 2N HCl aq., and the aqueous layer re-extracted. Organic extracts were combined and evaporated under a stream of nitrogen then purified using aminopropyl SPE (eluting with acetic acid:methanol:DCM, 1:2:2) to give the title compound as a white solid in >95% purity (0.041 g, 60%). NMR δH (400 MHz, d4-MeOD) 1.20 (t, 3H, J=7 Hz), 4.03 (q, 2H, J=7 Hz), 4.73 (q, 2H, J=8.5 Hz), m/z 297 [MH+].

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in anhydrous THF (2.5 ml)
  3. customthe reaction mixture degassed
  4. stirringthen stirred at ambient temperature for 72 h
  5. customThe mixture was partitioned between chloroform and 2N HCl aq.
  6. extractionthe aqueous layer re-extracted
  7. customevaporated under a stream of nitrogen
  8. customthen purified
  9. washaminopropyl SPE (eluting with acetic acid:methanol:DCM, 1:2:2)

Sources & evidence

ORD record
ord-7bc87e5077ea4422aef18bed41332fc6
Source dataset
uspto-grants-2013_03
Patent number
US08394808B2

Reaction notes

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