Benzyl Bromide → HCID 59395754, compound

HRID 1097637Notes

Reaction equation

HRID 1097637 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].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN(C(C)C)C(C)C.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]([CH2:19][CH2:20][CH2:21][C:22]2[N:26]=[CH:25][N:24]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:23]=2)[C:6]1=[O:28])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 178456318HCID 178456318, compound

Product 1

HCID 59395754HCID 59395754, compoundYield 2.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

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 (300 mg, 0.77 mmol) in anhydrous THF (5 ml) was treated with benzyl bromide (144 mg, 0.84 mmol) and DIPEA (147 μl, 0.84 mmol). The mixture was left to stir at rt under nitrogen for 4 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 was purified by a silica SPE column using a 0.5-5% MeOH/DCM gradient. The product fractions were combined and concentrated under high vacuum. The product was dissolved in THF (5 ml) then Pd(PPh3)4 (88 mg, 0.077 mmol) and morpholine (670 μl, 7.67 mmol) were added and the mixture left to stir at rt under nitrogen for 3 h. 88 mg of Pd(PPh3)4 (0.077 mmol) was added and the mixture was left to stir at rt under nitrogen for 16 h. The mixture was partitioned between EtOAc and H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc (×2). The organic layers were combined, washed with brine, dried (MgSO4) and concentrated. The crude product was purified by MDAP to give the title compound as a white solid (9 mg, 2%).

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 was purified by a silica SPE column
  8. concentrationconcentrated under high vacuum
  9. dissolutionThe product was dissolved in THF (5 ml)
  10. waitthe mixture left
  11. stirringto stir at rt under nitrogen for 3 h
  12. waitthe mixture was left
  13. stirringto stir at rt under nitrogen for 16 h
  14. customThe mixture was partitioned between EtOAc and H2O
  15. customThe organic layer was separated
  16. extractionthe aqueous layer was extracted with EtOAc (×2)
  17. washwashed with brine
  18. dry with materialdried (MgSO4)
  19. concentrationconcentrated
  20. customThe crude product was purified by MDAP

Sources & evidence

ORD record
ord-f71b253f6ac94ba2abf52d49be284e12
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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