Methyl iodide → 2-((6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile

HRID 1515146Notes

Reaction equation

HRID 1515146 reaction equation
[Cl:1][C:2]1[N:7]([CH2:8][C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])[C:6](=[O:17])[NH:5][C:4](=[O:18])[CH:3]=1.[H-].[Na+].[Li+].[Br-].I[CH3:24]>CN(C=O)C>[Cl:1][C:2]1[N:7]([CH2:8][C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])[C:6](=[O:17])[N:5]([CH3:24])[C:4](=[O:18])[CH:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 113574682-((6-Chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile

Product 1

HCID 113464162-((6-Chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrileYield 72.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) solution of benzylated 6-chlorouracil 2 (10 g, 38 mmol) in DMF-TH-F (1:1, 300 mL) under nitrogen, was added NaH (60%, 1.6 g, 39.9 mmol) in portions, followed by adding LiBr (2 g). The mixture was stirred at RT for 20 min. After adding iodomethane (5.4 mL, 76 mmol), the flask was sealed and stirred at this temperature for 10 min, RT for 2 h, and 35° C. overnight, and then concentrated in vacuo. The residue was dissolved in CHCl3 and washed with water and brine, dried (Na2SO4), and filtered then concentrated in vacuo. The crude product was crystallized from THF-Hexanes to give 7.6 g (72%) of the title compound 3. 1H NMR (400 MHz, DMSO): δ 7.87 (d, 1H, J=7.6 Hz), 7.70 (t, 1H, J=7.6 Hz), 7.51 (t, 1H, J=7.6 Hz), 7.40 (d, 1H, J=8 Hz), 6.21 (s, 1H), 5.38 (s, 2H), 3.28 (s, 3H). MS (ES) [m+H] calc'd for C13H11ClN3O2, 276.1; found 276.1.

Workup

  1. customthe flask was sealed
  2. stirringstirred at this temperature for 10 min, RT for 2 h
  3. concentration35° C. overnight, and then concentrated in vacuo
  4. dissolutionThe residue was dissolved in CHCl3
  5. washwashed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationthen concentrated in vacuo
  9. customThe crude product was crystallized from THF-Hexanes

Sources & evidence

ORD record
ord-1bab789040db48b09a8bc4a66e808e8c
Source dataset
uspto-grants-2012_07
Patent number
US08222411B2

Reaction notes

Loading…