Dimethylformamide → 3-{3-[Cyano-(5-isopropyl-2,6-dimethoxy-pyrimidin-4-yl)-methyl]-5-methyl-phenyl}-acrylonitrile
Reaction equation
Cl[C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([O:13][CH3:14])[N:3]=1.Br[CH2:16][C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][C:26]#[N:27])[CH:20]=[C:21]([CH3:23])[CH:22]=1.[H-].[Na+].[Cl-].[NH4+].[CH3:32][N:33](C=O)C>>[C:32]([CH:16]([C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([O:13][CH3:14])[N:3]=1)[C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][C:26]#[N:27])[CH:20]=[C:21]([CH3:23])[CH:22]=1)#[N:33]Participants
Reactant 5
Product 1
Procedure
To a stirred mixture of 4-chloro-5-isopropyl-2,6-dimethoxy-pyrimidine (7.12 g, 32.88 mmol) and 3-(3-bromomethyl-5-methyl-phenyl)-acrylonitrile (5.7 g, 31.21 mmol) in anhydrous DMF (60 ml) at 0° C. (ice bath) under nitrogen atmosphere, was portionwise added 60% sodium hydride (2.76 g, 68.88 mmol). After stirring for 1 hr., the mixture was further stirred at room temperature for overnight. The mixture was then neutralized with aqueous saturated ammonium chloride solution and the crude product was extracted with ether and purified by silica gel column chromatography (eluent, EA: hexanes (from 1:4 to 1:2)) to afford 1.8 g (16%) of a pale yellow foam. 1H NMR (300 MHz, CDCl3) δ 1.12 (3H, d, J=6.9 Hz), 1.15 (3H, d, J=6.9 Hz), 2.37 (3H, s), 3.02 (1H, m), 4.01 (6H, s), 5.39 (1H, s), 5.87 (1H, d, J=16.5 Hz), 7.23 (1H, s), 7.25 (1H, s), 7.27 (1H, s), 7.33 (1H, d, J=16.5 Hz).
Workup
- stirring, the mixture was further stirred at room temperature for overnight
- extractionthe crude product was extracted with ether
- custompurified by silica gel column chromatography (eluent, EA: hexanes (from 1:4 to 1:2))
Sources & evidence
- ORD record
- ord-121e4c55bbf04429b888af7e32f8a2dc
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08106064B2
Reaction notes
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