Hydrochloric Acid → ethyl 5-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)pentanoate

HRID 1097701Notes

Reaction equation

HRID 1097701 reaction equation
[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[N:10](CC=C)[C:9]=2[C:8](=[O:18])[NH:7][C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].N1CCOCC1.Cl>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.O.CCOC(C)=O>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 10796Cesium carbonateHCID 84580Ethyl 5-bromovalerateHCID 592995823-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 59395413ethyl 5-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)pentanoateYield 77.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (1.5 g, 5.31 mmol) in dry DMF (25 ml) was added Cs2CO3 (1.905 g, 5.84 mmol), followed by ethyl 5-bromovalerate (1.46 g, 6.99 mmol). The mixture was heated at 55° C. for 18 h then allowed to cool. It was degassed by repeatedly evacuating and readmitting nitrogen, then morpholine (3.70 ml, 42.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.0 g, 0.865 mmol) were added and the mixture stirred for 5 h. EtOAc (75 ml), 2M HCl (40 ml) and water (20 ml) were added and the organic phase was separated, washed with brine (3×25 ml), filtered to remove some insoluble yellow solid, dried (Na2SO4) and evaporated. The residue (2.5 g) was purified by aminopropyl SPE (20 g), loading in THF-MeOH (1:1), washing with MeOH and eluting the product with DCM-MeOH (1:1) containing 5% added AcOH to afford the title compound (1.53 g).

Workup

  1. temperatureto cool
  2. customIt was degassed
  3. customby repeatedly evacuating
  4. customthe organic phase was separated
  5. washwashed with brine (3×25 ml)
  6. filtrationfiltered
  7. customto remove some insoluble yellow solid
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customThe residue (2.5 g) was purified by aminopropyl SPE (20 g)
  11. washwashing with MeOH
  12. washeluting the product with DCM-MeOH (1:1)
  13. additioncontaining 5%
  14. additionadded AcOH

Sources & evidence

ORD record
ord-a8039d10e13841859bb60a3cfbf42b4c
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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