Sodium hydride → 3-[Cyano-(2,6-dimethoxy-5-nitro-pyrimidin-4-yl)-methyl]-5-methyl-benzonitrile

HRID 426268Notes

Reaction equation

HRID 426268 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([O:13][CH3:14])[N:3]=1.[C:15]([CH2:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:21]#[N:22])#[N:16].[H-].[Na+]>CN(C=O)C>[C:15]([CH:17]([C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([O:13][CH3:14])[N:3]=1)[C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:21]#[N:22])#[N:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 34135084-Chloro-2,6-dimethoxy-5-nitropyrimidineHCID 667054463-(Cyanomethyl)-5-methylbenzonitrile

Product 1

HCID 591848183-[Cyano-(2,6-dimethoxy-5-nitro-pyrimidin-4-yl)-methyl]-5-methyl-benzonitrileYield 98.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-Chloro-2,6-dimethoxy-5-nitro-pyrimidine (0.45 g, 2.05 mmol, 1.05 eq., prepared according to Cushman et al. J. Org. Chem. 2004, 69, 601-612) and 3-cyanomethyl-5-methyl-benzonitrile (0.305 g, 1.95 mmol, 1.0 eq.) was dissolved in DMF (3.36 mL) and cooled to 0° C. 60% Sodium hydride (0.157 g, 3.92 mmol, 2.0 eq.) was added portionwise and the reaction was stirred at 0° C. for 1 h, then rt for 1 h. The reaction was cooled to 0° C. and quenched with saturated ammonium chloride solution. The pH was adjusted to ˜6.0 with 1N HCl and mixture was extracted with ethyl ether. The organic layer was washed with water (2×), dried (MgSO4) and concentrated. The resulting residue was purified by flash column chromatography (silica gel, 20 to 50% ethyl acetate/hexane) to give a yellow foam (0.6514 g, 98%). 1H NMR (300 MHz, CDCl3): δ 7.56 (s, 1H), 7.54 (s, 1H), 7.40 (s, 1H), 5.64 (s, 1H), 4.05 (s, 6H), 2.34 (s, 3H). Mass spectrum: 338.0 (M−H)−.

Workup

  1. waitrt for 1 h
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with saturated ammonium chloride solution
  4. extractionwas extracted with ethyl ether
  5. washThe organic layer was washed with water (2×)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash column chromatography (silica gel, 20 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4bbe8757927e4d15868cacf7c91521dd
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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