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

HRID 602353

Reaktionsgleichung

Reaktionsgleichung von HRID 602353
[Cl:1][C:2]1[NH:7][C:6](=[O:8])[NH:5][C:4](=[O:9])[CH:3]=1.[H-].[Na+].[Br-].[Li+].Br[CH2:15][C:16]1[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=1.[H-].[Li+].[Li+].[I-].[Na+].[I-]>CN(C=O)C.CS(C)=O.CN(C=O)C.C1COCC1.CS(C)=O>[Cl:1][C:2]1[N:7]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]#[N:23])[C:6](=[O:8])[NH:5][C:4](=[O:9])[CH:3]=1

Komponenten

12

Edukt 7

HCID 5238Sodium IodideHCID 24758Sodium hydride2×HCID 62714Lithium hydrideHCID 66321Lithium iodideHCID 732726-ChlorouracilHCID 82050Lithium Bromide2×HCID 895992-(Bromomethyl)benzonitrile

Produkt 1

HCID 113574682-((6-Chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrileAusbeute 59,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 679Dimethyl SulfoxideLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 3013483N,N-dimethylformamide; methylsulfinylmethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 6-chlorouracil (20 g, 122 mmol) in a mixture of DMF-DMSO (6:1, 600 mL) under nitrogen at 0° C., was added sodium hydride (60%, 5.5 g, 137 mmol) in portions. After 0.5 h, lithium bromide (8 g, 96 mmol) was added into the mixture and stirred for 15 min at 0° C. A solution of α-Bromo-o-tolunitrile (25.1 g, 128 mmol) in DMF (30 mL) was added dropwise, and stirred at this temperature for 1 h, and then RT overnight. It will be understood that alkylation of the amine may be performed under standard conditions known in the art, including the use of a base such as NaH, LiH or the like in an organic solvent or mixture of solvents. The solvent may include DMSO, THF, DMF and the like, or mixtures thereof. In addition, additives may be used, including LiBr, LiI, NaI and the like. The mixture was evaporated and co-evaporated with water in vacuo to remove most of the DMF, and then poured into ice water (1 L). The precipitate was collected by filtration. The crude product was suspended in hot AcOEt-CHCl3 and sonicated for 5 min, allowed to stand at 0° C. for 1 h, and then filtered to give a white solid of the title compound (19 g) in 54% yield. It will also be understood by those skilled in the art that purification may be accomplished using various methods known in the art, including washing with an aqueous/organic solvent or mixture of solvents, recrystallization and/or column chromatography. Non-limiting examples of organic solvents and solvent mixtures may include ethyl acetate, isopropyl acetate, acetone, THF and the like. 1H-NMR (400 MHz, DMSO): δ 11.82 (s, 1H), 7.87 (d, 1H, J=7.6 Hz), 7.71 (t, 1H, J=7.6 Hz), 7.51 (t, 1H, J=7.6 Hz), 7.37 (d, H, J=8 Hz), 6.06 (s, 1H), 5.31 (s, 2H). MS (ES) [m+H] calc'd for C12H9ClN3O2, 262.0; found 262.0.

Aufarbeitung

  1. stirringstirred at this temperature for 1 h
  2. customRT overnight
  3. additionthe like in an organic solvent or mixture of solvents
  4. customThe mixture was evaporated
  5. customto remove most of the DMF
  6. additionpoured into ice water (1 L)
  7. filtrationThe precipitate was collected by filtration
  8. customsonicated for 5 min
  9. waitto stand at 0° C. for 1 h
  10. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-f6b36d53ee2e431a9549be5a13194079
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07906523B2

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