Dimethylformamide → 3-butyl-1-methyl-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purine-8-carbaldehyde

HRID 2386617Notes

Reaction equation

HRID 2386617 reaction equation
[CH2:1]([N:5]1[C:13]2[N:12]=[CH:11][N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CN([CH:33]=[O:34])C>C1COCC1>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([CH:33]=[O:34])[N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 2733832Lithium HexamethyldisilazideHCID 592995393-butyl-1-methyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 592995903-butyl-1-methyl-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purine-8-carbaldehydeYield 105.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

A pre-dried flask was charged with 3-butyl-1-methyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (300 mg, 1.14 mmol) and anhydrous THF (6 ml), cooled to −75° C. under nitrogen, then treated with LiHMDS (1.37 ml of a 1.0M solution in THF). The resulting solution was allowed to warm to −60° C. over 1.5 hours before the addition of anhydrous DMF (177 ul, 2.29 mmol). The solution was allowed to warm to −10° C. over 3 hours then it was quenched with sat. NH4Cl (aq) solution. The mixture was partitioned between 1M HCl (aq) and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated giving a brown oil (350 mg). The product was purified by SPE (Si, 10 g) eluting with EtOAc/cyclohexane mixtures to give the title compound as a white solid (131 mg, 39%); NMR; δH (400 MHz, d6-DMSO) 0.91 (t, 3H, J=7.5 Hz), 1.28-1.39 (m, 2H), 1.63-1.73 (m, 2H), 3.25 (s, 3H), 4.02 (t, 2H, J=7.5 Hz), 5.03 (dd, 1H, J=17 and 1 Hz), 5.17 (dd, 1H, J=10 and 1 Hz), 5.31 (app. d, 2H, J=5.5 Hz), 5.98-6.09 (m, 1H), 9.88 (s, 1H).

Workup

  1. temperatureto warm to −10° C. over 3 hours
  2. customit was quenched with sat. NH4Cl (aq) solution
  3. customThe mixture was partitioned between 1M HCl (aq) and EtOAc
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e876c8b40749478496eb5bf485738a02
Source dataset
uspto-grants-2012_09
Patent number
US08268839B2

Reaction notes

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