3-Acetylpyridine → 2-(2-Methyl-5-nitroanilino)-4-(3-pyridyl)pyrimidine

HRID 2243410Notes

Reaction equation

HRID 2243410 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=O)[CH3:2].[CH3:10]OC(OC)N(C)C.[N+]([O-])(O)=O.[CH3:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][C:24]=1[NH:32][C:33]([NH2:35])=[NH:34].[OH-].[Na+]>O.CO>[CH3:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][C:24]=1[NH:32][C:33]1[N:35]=[C:1]([C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:2]=[CH:10][N:34]=1

Participants

7

Reactant 4

HCID 95893-AcetylpyridineHCID 14798Sodium HydroxideHCID 78373Dimethylformamide dimethyl acetalHCID 178426711HCID 178426711, compound

Product 1

HCID 106861492-(2-Methyl-5-nitroanilino)-4-(3-pyridyl)pyrimidineYield 73.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Procedure

26.60 g of 3-acetylpyridine (0.219 mol; 1 eq.) and 44.0 mL of N,N-dimethylformamide dimethyl acetal (39.47 g; 0.331 mol; 1.508 eq.) were placed in a reactor flask and the mixture was refluxed for 1.5 h. Methanol, produced in the reaction was removed by distillation and the mixture was refluxed for further 2 hours. The rest of methanol and excess of the acetal were removed by distillation under slightly reduced pressure. The hot residue was treated with 100 mL DMF, and, after cooling down, with 56.3 g of 1-(2-methyl-5-nitrophenyl)guanidine nitrate (0.219 mol; 1 eq.). A solution of 8.8 g of sodium hydroxide in 17 mL of water was then added dropwise and the mixture was refluxed for 8 hours in an oil bath. Water (200 mL) was added with care to the hot solution, and the contents of the flask were poured to 700 mL of warm water. The whole mixture was cooled with stirring to room temperature. The precipitated solid was isolated by filtration and dried in the air to afford 49.41 g of crude 2-(2-methyl-5-nitroanilino)-4-(3-pyridinyl)pyrimidine (yield 73.2% calculated on 3-acetylpyridine), m.p. 186-188° C.; 1H NMR (DMSO-d6, 200 MHz): 2.43 (3H, s, CH3), 7.54 (3H, m, 3-H phenyl +5-H pyrimidine +5-H pyridyl), 7.90 (1H, dd, J=8.2, 2.2 Hz, 4-H phenyl), 8.48 (1H, dt, J1=7.9 Hz, 4-H pyridyl), 8.62 (1H, d, J=5.4 Hz, 6-H pyrimidine), 8.71 (1H, dd, 6-H pyridyl), 8.79 (1H, d, J=2.2 Hz, 6-H phenyl), 9.27 (1H, s, NH), 9.32 (1H, d, J=1.6 Hz, 2-H pyridyl).

Workup

  1. temperaturethe mixture was refluxed for 1.5 h
  2. customwas removed by distillation
  3. temperaturethe mixture was refluxed for further 2 hours
  4. customThe rest of methanol and excess of the acetal were removed by distillation under slightly reduced pressure
  5. additionThe hot residue was treated with 100 mL DMF
  6. temperaturethe mixture was refluxed for 8 hours in an oil bath
  7. temperatureThe whole mixture was cooled
  8. customThe precipitated solid was isolated by filtration
  9. customdried in the air

Sources & evidence

ORD record
ord-40ab9d29e1c94b2fb77c0881b531f119
Source dataset
uspto-grants-2010_03
Patent number
US07674901B2

Reaction notes

Loading…