Diethyl Oxalate → 9-Hydroxy-7-isopropyl-2-(2-propenyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,6,8(7H)-trione

HRID 1162810Notes

Reaction equation

HRID 1162810 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10](=[O:15])[NH:11][CH:12]([CH3:14])[CH3:13])[CH2:6][C:5]1=[O:16])[CH:2]=[CH2:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:27](OCC)(=[O:33])[C:28](OCC)=[O:29]>CN(C=O)C.C1COCC1>[OH:33][C:27]1[C:28](=[O:29])[N:11]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:15])[N:7]2[CH2:8][CH2:9][N:4]([CH2:1][CH:2]=[CH2:3])[C:5](=[O:16])[C:6]=12

Participants

6

Reactant 3

HCID 7268Diethyl OxalateHCID 2733832Lithium Hexamethyldisilazide2×HCID 684331521-(2-propenyl)-4-(N-2-propylcarbamoyl)-2-piperazinone

Product 1

HCID 684317659-Hydroxy-7-isopropyl-2-(2-propenyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,6,8(7H)-trione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1-(2-propenyl)-4-(N-2-propylcarbamoyl)-2-piperazinone (8.0 g, 35 mmol) in DMF (80 mL) at 0° C. was added lithium bis(trimethylsily)amide (40 mL of a 1.0 M solution in THF, 40 mmol). Diethyl oxalate (5.84 g, 40 mmol) was added and the mixture was stirred for 1 h at 0° C. More lithium bis(trimethylsily)amide was added (35 mL of a 1.0 M solution in THF, 35 mmol) and the mixture was stirred for 1 h at 0° C., and then at ambient temperature for 18 h. The reaction was quenched by the addition of 0.5 N aqueous HCl to pH 3 and the solvents were removed in vacuo. The residue was vigorously stirred in methanol-water, and the precipitate was collected by filtration and dried in vacuo to give the title compound. HPLC RT=2.72 min (Method A); ES MS (M+H)=280; 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 5.80 (ddt, 1H), 5.29 (d, J=17 Hz, 1H), 5.22 (d, J=10 Hz, 1H), 5.05 (septet, J=7 Hz, 1H), 4.10 (d, J=7 Hz, 2H), 3.94 (t, J=7 Hz), 3.58 (t, J=7 Hz, 2H), 1.38 (d, J=7 Hz, 6H).

Workup

  1. stirringwas stirred for 1 h at 0° C.
  2. waitat ambient temperature for 18 h
  3. customThe reaction was quenched by the addition of 0.5 N aqueous HCl to pH 3
  4. customthe solvents were removed in vacuo
  5. stirringThe residue was vigorously stirred in methanol-water
  6. filtrationthe precipitate was collected by filtration
  7. customdried in vacuo

Sources & evidence

ORD record
ord-e46fc67ac0a94b72a8dba16e43f86431
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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