Dimethylformamide → 4-Chloro-3-(5-isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzonitrile

HRID 2194792Notes

Reaction equation

HRID 2194792 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.[Cl:15][C:16]1[C:23]([CH3:24])=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=1[CH2:25]C#N.[H-].[Na+].CN(C=[O:34])C>>[Cl:15][C:16]1[C:23]([CH3:24])=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=1[C:25]([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)=[O:34]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 160881865-Isopropyl-6-chloro-2,4-dimethoxypyrimidineHCID 670504934-Chloro-3-cyanomethyl-5-methyl-benzonitrile

Product 1

HCID 582034604-Chloro-3-(5-isopropyl-2,6-dimethoxy-pyrimidine-4-carbonyl)-5-methyl-benzonitrileYield 11%

Procedure

To a solution of 4-chloro-5-isopropyl-2,6-dimethoxy-pyrimidine (0.442 g, 2.04 mmol) and 4-chloro-3-cyanomethyl-5-methyl-benzonitrile (0.3707 g, 1.94 mmol) in DMF at 0° C. was added NaH portionwise over 15 minutes to give an orange-red reaction mixture. After stirring for 24 hr, O2 was bubbled into the reaction mixture for 36 hr. The reaction mixture was quenched with saturated ammonium chloride solution and methanol, and diluted with ethyl acetate. The organic layer was washed with saturated ammonium chloride solution, H2O, saturated ammonium chloride solution and dried (MgSO4), then concentrated and purified by flash column chromatography (silica gel, 5 to 50% ethyl acetate/hexane) to give title compound (0.0767 g, 11%). 1H NMR (300 MHz, CDCl3): 7.67 (s, 1H), 7.59 (s, 1H), 4.00 (s, 3H), 3.75 (s, 3H), 3.3-3.2 (m, 1H), 2.37 (s, 3H), 1.25 (s, 3H), 1.23 (s, 3H); 13C NMR (75 MHz, CDCl3): 192.8, 171.1, 162.2, 160.2, 139.1, 138.9, 137.3, 135.9, 132.3, 119.9, 117.4, 110.8, 54.7, 54.2, 26.5, 20.2, 20.2; Mass Spectrum: 360.2, 362.1 (M+H).

Workup

  1. customto give an orange-red reaction mixture
  2. customO2 was bubbled into the reaction mixture for 36 hr
  3. customThe reaction mixture was quenched with saturated ammonium chloride solution and methanol
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with saturated ammonium chloride solution, H2O, saturated ammonium chloride solution
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 5 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-dd98bc5db1094aaa96c2faeca4666dd3
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

Loading…