Dimethylformamide → 3-[3-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile

HRID 426169Notes

Reaction equation

HRID 426169 reaction equation
C([CH:3]([C:15]1[C:20]([CH:21]([CH3:23])[CH3:22])=[C:19]([O:24][CH3:25])[N:18]=[C:17]([O:26][CH3:27])[N:16]=1)[C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]#[N:14])[CH:7]=[C:8]([CH3:10])[CH:9]=1)#N.[H-].[Na+].CN(C=[O:34])C>>[CH:21]([C:20]1[C:15]([C:3]([C:4]2[CH:5]=[C:6]([CH:11]=[CH:12][C:13]#[N:14])[CH:7]=[C:8]([CH3:10])[CH:9]=2)=[O:34])=[N:16][C:17]([O:26][CH3:27])=[N:18][C:19]=1[O:24][CH3:25])([CH3:23])[CH3:22]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 667056503-{3-[Cyano-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methyl]-5-methyl-phenyl}-acrylonitrile

Product 1

HCID 667055443-[3-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrileYield 77%

Procedure

To a stirred solution of 3-{3-[Cyano-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methyl]-5-methyl-phenyl}-acrylonitrile (96) (1.8 g, 4.97 mmol) in anhydrous DMF (20 ml) under nitrogen atmosphere, was added 60% sodium hydride (238 mg, 5.96 mmol). After 20 min., oxygen was bubbled into the reaction mixture for 3 hr. The mixture was partitioned between ether and aqueous saturated ammonium chloride solution. The organic layer was taken, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was then purified by silica gel column chromatography (eluent, EA:hexanes (1:4)) to afford 1.34 g (77%) of a white solid. m.p. 144-145° C.; 1H NMR (300 MHz, CDCl3) δ 1.19 (6H, d, J=6.9 Hz), 2.42 (3H, s), 2.83 (1H, m), 3.94 (3H, s), 4.08 (3H, s), 5.92 (1H, d, J=16.8 Hz), 3.39 (1H, d, J=16.8 Hz), 7.49 (1H, s), 7.69 (1H, s), 7.75 (1H, s).

Workup

  1. customoxygen was bubbled into the reaction mixture for 3 hr
  2. customThe mixture was partitioned between ether and aqueous saturated ammonium chloride solution
  3. washwashed with water twice
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was then purified by silica gel column chromatography (eluent, EA:hexanes (1:4))

Sources & evidence

ORD record
ord-e8f63d76116748c1b7f388cdc3989979
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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