Diethyl Oxalate → 2-[(4-Fluorophenyl)methyl]-9-hydroxy-7-methyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,6,8-trione

HRID 1162804Notes

Reaction equation

HRID 1162804 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([NH:15][CH3:16])=[O:14])[CH2:9][C:8]2=[O:17])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:30]([O:37]CC)(=O)[C:31]([O:33]CC)=O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]3[C:13](=[O:14])[N:15]([CH3:16])[C:31](=[O:33])[C:30]([OH:37])=[C:9]3[C:8]2=[O:17])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 7268Diethyl OxalateHCID 2733832Lithium HexamethyldisilazideHCID 684315454-(4-Fluorobenzyl)-N-methyl-3-oxopiperazine-1-carboxamide

Product 1

HCID 546922742-[(4-Fluorophenyl)methyl]-9-hydroxy-7-methyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,6,8-trione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-(4-Fluorobenzyl)-N-methyl-3-oxopiperazine-1-carboxamide (200 mg, 0.75 mmol) was dissolved in anhydrous DMF (1.5 mL) under nitrogen and chilled to 0° C. in an ice-water bath. Lithium bis(trimethylsilyl)amide (0.91 mL, 0.91 mmol, 1M solution in THF) was added dropwise and then diethyl oxalate (0.15 mL, 1.13 mmol) was immediately added. The reaction was allowed to warm to room temperature and stirred for one hour. The solvent was removed in vacuo and the residue partitioned between aqueous HCl and ethyl acetate. The layers were separated and the aqueous phase was extracted twice more with ethyl acetate. The combined organic extracts were concentrated in vacuo. The residue was triturated with ethyl acetate and the solids were collected by vacuum filtration to yield the title compound as an off-white solid. 1H NMR (400 MHz, d6 DMSO) δ 11.82 (bs, 1H), 7.40 (m, 2H), 7.21 (m, 2H), 4.69 (s, 2H), 3.94 (m, 2H), 3.58 (m, 2H), and 3.21 (s, 3H). HRMS (FT-ICR) C15H14FN3O4+H=320.1047; calculated 320.1041.

Workup

  1. temperatureto warm to room temperature
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between aqueous HCl and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted twice more with ethyl acetate
  6. concentrationThe combined organic extracts were concentrated in vacuo
  7. customThe residue was triturated with ethyl acetate
  8. filtrationthe solids were collected by vacuum filtration

Sources & evidence

ORD record
ord-2cc9d3eee1804523a8c93f997302bb3a
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

Loading…