Morpholine → HCID 59395800, compound

HRID 1097640Notes

Reaction equation

HRID 1097640 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])[N:7]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[N:24]=[CH:25][NH:26]C=2)[C:6]1=[O:28])[CH2:2][CH2:3][CH3:4].Cl[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]([F:40])([F:39])[F:38].CCN(C(C)C)C(C)C.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>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:19][CH2:20][CH2:21][C:22]2[N:26]=[CH:25][N:24]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]([F:38])([F:39])[F:40])[CH:23]=2)[C:6]1=[O:28])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 890281-(Chloromethyl)-2-(trifluoromethyl)benzeneHCID 178456318HCID 178456318, compound

Product 1

HCID 59395800HCID 59395800, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-butyl-8-chloro-1-[4-(1H-imidazol-4-yl)butyl]-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (150 mg, 0.38 mmol) in anhydrous DMF (3 ml) was treated with 1-(chloromethyl)-2-(trifluoromethyl)benzene (61 μl, 0.42 mmol) and DIPEA (73 μl, 0.42 mmol). The mixture was left to stir at rt under nitrogen for 3 days. The mixture was partitioned between EtOAc and 2M HCl (aq). The organic layer was separated, washed with brine, dried (MgSO4) and concentrated. The crude product was purified on a silica SPE column using DCM to load the material onto the column and wash through the impurities then a 0-5% MeOH/DCM gradient to elute the compound. The product fractions were combined and concentrated and the residues dissolved in anhydrous DMF (3 ml). The solution was degassed then Pd(PPh3)4 (35 mg, 0.030 mmol) and morpholine (174 μl, 2.0 mmol) were added and the mixture left to stir at rt under nitrogen for 3 h. The crude product was purified by an aminopropyl SPE using MeOH to load the compound onto the column and wash through the impurities then a 0-5% AcOH/MeOH gradient to elute the product. The product fractions were combined and concentrated by high vacuum to leave the title compound as a white solid (50 mg, 26%).

Workup

  1. waitThe mixture was left
  2. customThe mixture was partitioned between EtOAc and 2M HCl (aq)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified on a silica SPE column
  8. washwash through the impurities
  9. washa 0-5% MeOH/DCM gradient to elute the compound
  10. concentrationconcentrated
  11. dissolutionthe residues dissolved in anhydrous DMF (3 ml)
  12. customThe solution was degassed
  13. waitthe mixture left
  14. stirringto stir at rt under nitrogen for 3 h
  15. customThe crude product was purified by an aminopropyl SPE
  16. washwash through the impurities
  17. washa 0-5% AcOH/MeOH gradient to elute the product
  18. concentrationconcentrated by high vacuum

Sources & evidence

ORD record
ord-c655536c5b7a4f6389d62a682176ddf1
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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