Dimethylformamide → (3-Bromo-5-methyl-phenyl)-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methanone

HRID 2194747Notes

Reaction equation

HRID 2194747 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]([C:12]2[C:17]([CH:18]([CH3:20])[CH3:19])=[C:16]([O:21][CH3:22])[N:15]=[C:14]([O:23][CH3:24])[N:13]=2)C#N)[CH:5]=[C:6]([CH3:8])[CH:7]=1.[H-].[Na+].CN(C=[O:31])C>>[Br:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[C:17]([CH:18]([CH3:20])[CH3:19])=[C:16]([O:21][CH3:22])[N:15]=[C:14]([O:23][CH3:24])[N:13]=2)=[O:31])[CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 596868362-(3-Bromo-5-methylphenyl)-2-(5-isopropyl-2,6-dimethoxypyrimidin-4-YL)acetonitrile

Product 1

HCID 59686860(3-Bromo-5-methyl-phenyl)-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methanoneYield 89%

Procedure

To a stirred solution of (3-bromo-5-methyl-phenyl)-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-acetonitrile (40 g, 0.1 M) in anhydrous DMF (300 mL) in a water bath under an atmosphere of nitrogen, was added 60% sodium hydride (4.92 g, 0.12 M) in portions. After 30 min, oxygen gas was bubbled into the reaction mixture for 2 hr. The mixture was neutralized with aqueous saturated ammonium chloride solution. The crude product was extracted with ether and purified by silica gel column chromatography (eluent, ether:hexanes (1:9)) to afford 34.6 g (89%) of a white solid. m.p. 122-123° C.; 1H NMR (200 MHz, CDCl3) δ 1.17 (6H, d, J=7.1 Hz), 2.36 (3H, s), 2.77 (1H, m), 3.92 (3H, s), 4.05 (3H, s), 7.54-7.56 (2H, m), 7.75 (1H, m).

Workup

  1. customoxygen gas was bubbled into the reaction mixture for 2 hr
  2. extractionThe crude product was extracted with ether
  3. custompurified by silica gel column chromatography (eluent, ether:hexanes (1:9))

Sources & evidence

ORD record
ord-02aa1c28768048cdb0c5bb0f9af0db96
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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