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

HRID 1515145Notes

Reaction equation

[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>CN(C=O)C.CS(C)=O.CN(C=O)C>[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

Participants

Conditions

Temperature: 0 °C

Procedure

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. 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. 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, 1H, J=8 Hz), 6.06 (s, 1H), 5.31 (s, 2H). MS (ES) [m+H] calc'd for C12H9ClN3O2, 262.0; found 262.0.

Workup

stirringstirred at this temperature for 1 h
customRT overnight
customThe mixture was evaporated
customto remove most of the DMF
additionpoured into ice water (1 L)
filtrationThe precipitate was collected by filtration
customsonicated for 5 min
waitto stand at 0° C. for 1 h
filtrationfiltered

Sources & evidence

ORD record: ord-a7c34ce2dd96429da0b2ef14f7b31a79
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222411B2

Reaction notes

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