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

HRID 1097669Notes

Reaction equation

HRID 1097669 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:20]1([CH2:26][C:27]2[N:31]=[C:30]([CH2:32][CH2:33][CH2:34]O)[O:29][N:28]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1.N1CCOCC1>C1COCC1.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>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:34][CH2:33][CH2:32][C:30]2[O:29][N:28]=[C:27]([CH2:26][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:31]=2)[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 8083MorpholineHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 592995823-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dioneHCID 593955733-[3-(Phenylmethyl)-1,2,4-oxadiazol-5-yl]-1-propanol

Product 1

HCID 593958743-Butyl-8-chloro-1-{3-[3-(phenylmethyl)-1,2,4-oxadiazol-5-yl]propyl}-3,7-dihydro-1H-purine-2,6-dioneYield 23.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (205 mg, 0.73 mmol) in anhydrous THF (4 ml) was treated with 3-[3-(phenylmethyl)-1,2,4-oxadiazol-5-yl]-1-propanol (190 mg, 0.87 mmol) and PPh3 (247 mg, 0.94 mmol). DBAD (217 mg, 0.94 mmol) was added in one portion and the mixture was stirred at rt under nitrogen for 18 h. The mixture was degassed by high vacuum then Pd(PPh3)4 (84 mg, 0.073 mmol) and morpholine (636 μl, 7.3 mmol) were added. The mixture was stirred at rt under nitrogen for 3 h. The mixture was partitioned between EtOAc and 2M HCl (aq) and the organic layer separated, washed with brine, dried (MgSO4) and concentrated. The crude material was purified by an aminopropyl column using MeOH to load the compound onto the column and wash through the impurities, then with 2-4% AcOH/MeOH gradient to remove the compound from the column. Further purification was effected by MDAP to give the title compound as a white solid (75 mg, 23%).

Workup

  1. customThe mixture was degassed by high vacuum
  2. stirringThe mixture was stirred at rt under nitrogen for 3 h
  3. customThe mixture was partitioned between EtOAc and 2M HCl (aq)
  4. customthe organic layer separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude material was purified by an aminopropyl column
  9. washwash through the impurities
  10. customwith 2-4% AcOH/MeOH gradient to remove the compound from the column
  11. customFurther purification

Sources & evidence

ORD record
ord-c2b30c7f9f654c3b9ccbf22ab0738fec
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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