Potassium Carbonate → 3-Butyl-8-chloro-1-{3-[3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl]propyl}-3,7-dihydro-1H-purine-2,6-dione

HRID 1097656Notes

Reaction equation

HRID 1097656 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]#[N:11].Cl.[NH2:13]O.C(=O)([O-])[O-].[K+].[K+].[CH2:21]([N:25]1[C:33]2[N:32]=[C:31]([Cl:34])[NH:30][C:29]=2[C:28](=[O:35])[N:27]([CH2:36][CH2:37][CH2:38][C:39](OCC)=[O:40])[C:26]1=[O:44])[CH2:22][CH2:23][CH3:24].[O-]CC.[Na+]>CCO.O>[CH2:21]([N:25]1[C:33]2[N:32]=[C:31]([Cl:34])[NH:30][C:29]=2[C:28](=[O:35])[N:27]([CH2:36][CH2:37][CH2:38][C:39]2[O:40][N:13]=[C:10]([CH2:9][C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])[N:11]=2)[C:26]1=[O:44])[CH2:22][CH2:23][CH3:24]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 5189682,3-DifluorophenylacetonitrileHCID 2723922Sodium ethoxideHCID 59395861Ethyl 4-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)butanoate

Product 1

HCID 593956853-Butyl-8-chloro-1-{3-[3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl]propyl}-3,7-dihydro-1H-purine-2,6-dioneYield 22.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

2,3-Difluorophenylacetonitrile (23 mg, 0.15 mmol) was dissolved in EtOH (1 ml). Hydroxylamine hydrochloride (14 mg, 0.20 mmol) was added, followed by water (0.5 ml) and potassium carbonate (41 mg, 0.3 mmol). The mixture was heated at reflux overnight and then cooled and partitioned between EtOAc and brine. The organic phase was evaporated and the crude amidoxime thus obtained was dissolved in EtOH (1 ml). Ethyl 4-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)butanoate (43 mg, 0.12 mmol) and 21% by wt. ethanolic sodium ethoxide ((0.067 ml, 0.18 mmol) was added and the mixture heated in the microwave reactor at 140° C. for 10 min. The mixture was partitioned between EtOAc and 2M HCl, the organic phase evaporated and the product purified by MDAP to provide the title compound as a solid (13 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. temperaturecooled
  4. custompartitioned between EtOAc and brine
  5. customThe organic phase was evaporated
  6. customthe crude amidoxime thus obtained
  7. customThe mixture was partitioned between EtOAc and 2M HCl
  8. customthe organic phase evaporated
  9. customthe product purified by MDAP

Sources & evidence

ORD record
ord-b079d49086ae41019873f7faac1e0528
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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