Sodium hydride → 2-(3-Bromo-5-methylphenyl)-2-(5-isopropyl-2,6-dimethoxypyrimidin-4-YL)acetonitrile

HRID 426180Notes

Reaction equation

HRID 426180 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:15][C:16]1[CH:17]=[C:18]([CH2:23][C:24]#[N:25])[CH:19]=[C:20]([CH3:22])[CH:21]=1.[H-].[Na+].[Cl-].[NH4+]>CN(C=O)C>[Br:15][C:16]1[CH:17]=[C:18]([CH:23]([C:2]2[C:7]([CH:8]([CH3:10])[CH3:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([O:13][CH3:14])[N:3]=2)[C:24]#[N:25])[CH:19]=[C:20]([CH3:22])[CH:21]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 160881865-Isopropyl-6-chloro-2,4-dimethoxypyrimidineHCID 236288332-(3-Bromo-5-methylphenyl)acetonitrile

Product 1

HCID 596868362-(3-Bromo-5-methylphenyl)-2-(5-isopropyl-2,6-dimethoxypyrimidin-4-YL)acetonitrileYield 87.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 4-chloro-5-isopropyl-2,6-dimethoxy-pyrimidine (47.63 g, 0.22M) and (3-bromo-5-methyl-phenyl)-acetonitrile (42 g, 0.2M) in anhydrous DMF (220 ml) in an ice-water bath under an atmosphere of nitrogen, was portionwise added 60% sodium hydride (16 g, 0.4M). After stirring for 1 hr., the mixture was stirred at room temperature for overnight. 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 (1:7)) to afford 68 g (87%) of a white solid. m.p. 123-124° C.; 1H NMR (200 MHz, CDCl3) δ 1.11 (3H, d, J=6.9 Hz), 1.15 (3H, D, J=6.9 Hz), 2.32 (3H, s), 2.97 (1H, m), 4.00 (3H, s), 4.01 (3H, s), 5.34 (1H, s), 7.14 (1H, s), 7.28 (1H, s), 7.31 (1H, s).

Workup

  1. stirring, the mixture was stirred at room temperature for overnight
  2. extractionThe crude product was extracted with ether
  3. custompurified by silica gel column chromatography (eluent, ether:hexanes (1:7))

Sources & evidence

ORD record
ord-d949b833af6c4e0fbd1294d421c55923
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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