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

HRID 602353

反応式

HRID 602353 の反応式
[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

参加物

12

反応物 7

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

生成物 1

HCID 113574682-((6-Chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile収率 59.5%

試薬・触媒・溶媒 4

HCID 679Dimethyl Sulfoxide溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 3013483N,N-dimethylformamide; methylsulfinylmethane溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f6b36d53ee2e431a9549be5a13194079
出典データセット
uspto-grants-2011_03
特許番号
US07906523B2

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