Oxygen → 3-(5-Cyclopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzonitrile

HRID 426253Notes

Reaction equation

HRID 426253 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[C:7]([CH:16]([C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21](C)[CH:20]=3)C#N)=[N:8][C:9]([O:14][CH3:15])=[N:10][C:11]=2[O:12][CH3:13])[CH2:5][CH2:4]1.[O:27]=O.C(OCC)(=O)C.[CH3:35][N:36](C=O)C>>[CH:3]1([C:6]2[C:7]([C:16]([C:19]3[CH:20]=[C:21]([CH:22]=[C:23]([CH3:25])[CH:24]=3)[C:35]#[N:36])=[O:27])=[N:8][C:9]([O:14][CH3:15])=[N:10][C:11]=2[O:12][CH3:13])[CH2:5][CH2:4]1

Participants

6

Reactant 5

HCID 977OxygenHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 66705526(5-Cyclopropyl-2,6-dimethoxy-pyrimidin-4-yl)-(3,5-dimethyl-phenyl)-acetonitrile

Product 1

HCID 591847753-(5-Cyclopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzonitrileYield 48%

Conditions

Temperature
0 °C

Procedure

At 0° C., NaH (60%, 9 mg, 0.4 mmol, 2 eq.) was added to (5-cyclopropyl-2,6-dimethoxy-pyrimidin-4-yl)-(3,5-dimethyl-phenyl)-acetonitrile (67 mg, 0.2 mmol) in 2 mL DMF solution. Oxygen balloon was applied. The reaction was stirred at 0° C. and warmed up to room temperature overnight. LC-MS shows the reaction complete. Ethyl acetate was added to the reaction mixture, followed by washing with brine. The organic layer was concentrated down and purified (silica gel, 0-50% EtOAc/hexane) to give white solid (31 mg, 48%). LC-MS shows 324.2 (M+1). 1H NMR (300 MHz, CDCl3): δ 7.98 (s, 1H), 7.90 (s, 1H), 7.63 (s, 1H), 4.05 (s, 3H), 3.93 (s, 3H), 2.43 (s, 3H), 1.53 (m, 1H), 0.77 (m, 2H), 0.42 (m, 2H).

Workup

  1. temperaturewarmed up to room temperature overnight
  2. customthe reaction complete
  3. washby washing with brine
  4. concentrationThe organic layer was concentrated down
  5. custompurified (silica gel, 0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-f142e469059c4ffb986c2b0d5b9aaa91
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

Loading…