Morpholine → HCID 59395489, compound

HRID 1097734Notes

Reaction equation

HRID 1097734 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][N:9]1[C:17](=[O:18])[C:16]2[N:15](CC=C)[C:14]([Cl:22])=[N:13][C:12]=2[N:11]([CH2:23][CH2:24][CH2:25][CH3:26])[C:10]1=[O:27])(=O)=O.C(=O)([O-])[O-].[K+].[K+].[CH2:34]([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.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>[CH2:23]([N:11]1[C:12]2[N:13]=[C:14]([Cl:22])[NH:15][C:16]=2[C:17](=[O:18])[N:9]([CH2:8][CH2:7][CH2:6][N:44]2[CH2:45][CH2:46][N:41]([CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:42][CH2:43]2)[C:10]1=[O:27])[CH2:24][CH2:25][CH3:26]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 759941-BenzylpiperazineHCID 59395634HCID 59395634, compound

Product 1

HCID 59395489HCID 59395489, compoundYield 24.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-[3-butyl-8-chloro-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purin-1-yl]propyl methanesulfonate (0.08 g, 0.19 mmol) in DMF (5 ml) was treated with potassium carbonate (0.08 g, 0.6 mmol) and 1-benzylpiperazine (0.04 g, 0.23 mmol) and then heated at 70° C. for 2 h. The mixture was cooled, evaporated to dryness and partitioned between 10 ml of DCM and 10 ml of water. The organic phase was evaporated to dryness and the residue dissolved in anhydrous THF (5 ml). The solution was cautiously degassed by the repeated application of vacuum to the reaction mixture and subsequent backfilling with nitrogen gas and then treated with tetrakis(triphenylphosphine)palladium(0) (0.010 g, 0.009 mmol) and morpholine (0.200 ml, 2.3 mmol) and the mixture stirred for 2 h in a nitrogen atmosphere. The mixture was evaporated and the residue taken up in 5 ml of methanol and added to a 2 g aminopropyl SPE cartridge which was then washed with methanol and the product eluted using a 3% solution of acetic acid in methanol. Product-containing fractions were pooled and evaporated to dryness. The product was then purified by flash chromatography using a gradient elution from DCM/2% Acetic acid to DCM/20% MeOH/2% Acetic acid and the final product freeze-dried from 1,4-dioxan to give the title compound as a white solid (0.021 g, 24%).

Workup

  1. temperatureThe mixture was cooled
  2. customevaporated to dryness
  3. custompartitioned between 10 ml of DCM and 10 ml of water
  4. customThe organic phase was evaporated to dryness
  5. dissolutionthe residue dissolved in anhydrous THF (5 ml)
  6. customThe solution was cautiously degassed by the repeated application of vacuum to the reaction mixture and subsequent backfilling with nitrogen gas
  7. customThe mixture was evaporated
  8. additionadded to a 2 g aminopropyl SPE cartridge which
  9. washwas then washed with methanol
  10. washthe product eluted
  11. customevaporated to dryness
  12. customThe product was then purified by flash chromatography
  13. washa gradient elution from DCM/2% Acetic acid to DCM/20% MeOH/2% Acetic acid
  14. dry with materialthe final product freeze-dried from 1,4-dioxan

Sources & evidence

ORD record
ord-4fedb4b1ddaa4df6b68531a9cdabd73a
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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