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

HRID 1515147Notes

Reaction equation

HRID 1515147 reaction equation
[Cl:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH3:9])[C:4](=[O:10])[CH:3]=1.C[N:12]1[CH2:16][CH2:15][CH2:14][C:13]1=O.C(N(C(C)C)CC)(C)C.[C:27]1(C)[CH:32]=CC=[CH:29][CH:28]=1>>[Cl:1][C:2]1[N:7]([CH2:13][C:14]2[CH:29]=[CH:28][CH:27]=[CH:32][C:15]=2[C:16]#[N:12])[C:6](=[O:8])[N:5]([CH3:9])[C:4](=[O:10])[CH:3]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 961416-chloro-3-methylpyrimidine-2,4(1H,3H)-dione

Product 1

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

Conditions

Temperature
65 °C

Procedure

To a solution of 6-chloro-3-methyluracil (1 equiv., 1 wt.), N-methylpyrrolidone (NMP; 4 vol.) and diisopropylethylamine (Hünig's base, 1.5 equiv., 1.21 wt.), was added a solution of α-bromotoluoylnitrile (1.1 equiv., 1.35 wt.) and toluene (4 vol.). The mixture was heated at 60-70° C. and agitated for 2-3 hrs, or until completion. The solution was then cooled to 20-30° C., quenched with deionized water (5 vol.) at less than 35° C., agitated for 30 min, cooled to 0-5° C., and then agitated for at least one hour. The resultant slurry was filtered, reslurried in isopropanol, displacement washed with isopropanol, and dried under vacuum at 55-60° C.

Workup

  1. temperatureThe solution was then cooled to 20-30° C.
  2. customquenched with deionized water (5 vol.) at less than 35° C.
  3. stirringagitated for 30 min
  4. temperaturecooled to 0-5° C.
  5. stirringagitated for at least one hour
  6. filtrationThe resultant slurry was filtered
  7. washdisplacement washed with isopropanol
  8. customdried under vacuum at 55-60° C.

Sources & evidence

ORD record
ord-1f1f974d4b134aef8b1484e964cc83bd
Source dataset
uspto-grants-2012_07
Patent number
US08222411B2

Reaction notes

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