Dimethylformamide → 5-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-isophthalonitrile

HRID 426279Notes

Reaction equation

HRID 426279 reaction equation
C([CH:3]([C:14]1[C:19]([CH:20]([CH3:22])[CH3:21])=[C:18]([O:23][CH3:24])[N:17]=[C:16]([O:25][CH3:26])[N:15]=1)[C:4]1[CH:5]=[C:6]([C:12]#[N:13])[CH:7]=[C:8]([CH:11]=1)[C:9]#[N:10])#N.[H-].[Na+].CN(C=[O:33])C>>[CH:20]([C:19]1[C:14]([C:3]([C:4]2[CH:5]=[C:6]([C:12]#[N:13])[CH:7]=[C:8]([CH:11]=2)[C:9]#[N:10])=[O:33])=[N:15][C:16]([O:25][CH3:26])=[N:17][C:18]=1[O:23][CH3:24])([CH3:22])[CH3:21]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 591847545-[Cyano-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methyl]-isophthalonitrile

Product 1

HCID 591847555-(5-Isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-isophthalonitrileYield 8%

Procedure

To a solution of 5-[cyano-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methyl]-isophthalonitrile (0.2457 g, 0.707 mmol) in DMF (2.4 mL) was added 60% sodium hydride (0.031 g, 0.778 mmol) and stirred for 30 min. Oxygen was bubbled into reaction mixture for 4 h. The reaction was quenched with saturated ammonium chloride solution and pH was adjusted to ˜6.0 with 1N HCl. Mixture was extracted with ethyl acetate and organic layer was washed with water (2×), dried (MgSO4) and concentrated. The resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane) to give a white foam (0.018 g, 8%). 1H NMR (300 MHz, CDCl3): δ 8.32 (s, 2H); 8.08 (s, 1H), 4.05 (s, 3H), 3.89 (s, 3H), 3.0-2.8 (m, 1H), 1.19 (s, 3H), 1.42 (s, 3H). Mass spectrum: 337.2 (M+H)+.

Workup

  1. customOxygen was bubbled into reaction mixture for 4 h
  2. customThe reaction was quenched with saturated ammonium chloride solution and pH
  3. extractionMixture was extracted with ethyl acetate and organic layer
  4. washwas washed with water (2×)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2559a60a066e421c91d01898dd4153f9
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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