p-Toluenesulfonic acid → 2-(2,6-Dimethylpyridin-4-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591803Notes

Reaction equation

HRID 591803 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]=O)[CH:5]=[C:4]([CH3:10])[N:3]=1.[NH2:11][C:12]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[C:17]([O:23][CH3:24])[C:13]=1[C:14]([NH2:16])=[O:15].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:16][C:14](=[O:15])[C:13]3[C:12](=[CH:20][C:19]([O:21][CH3:22])=[CH:18][C:17]=3[O:23][CH3:24])[N:11]=2)[CH:5]=[C:4]([CH3:10])[N:3]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 27630042,6-Dimethylpyridine-4-carbaldehydeHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 1359390642-(2,6-Dimethylpyridin-4-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2,6-dimethylpyridine-4-carbaldehyde (0.14 g, 1.00 mmol) in N,N-dimethyl acetamide (10 mL) were added 2-amino-4,6-dimethoxybenzamide (0.20 g, 1.00 mmol), sodium hydrogen sulfite (0.21 g, 2.00 mmol), and p-toluenesulfonic acid (0.28 g, 1.50 mmol). The reaction mixture was stirred at 110° C. for 16 hours under nitrogen. After cooling to room temperature, solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution (30 mL), water (30 mL), and brine (30 mL), and dried over anhydrous sodium sulfate. Solvent was evaporated, and the residue was purified by column chromatography (silica gel 230-400 mesh; 2-5% methanol in dichloromethane as eluent) to give the title compound as a yellow solid. Yield: 0.030 g (10%). MP 291-292° C. 1H NMR (400 MHz, CDCl3): δ 9.86 (br s, 1H), 7.60 (s, 2H), 6.87 (d, J=2.2 Hz, 1H), 6.53 (d, J=2.2 Hz, 1H), 3.99 (s, 3H), 3.95 (s, 3H), 2.66 (s, 6H). MS (ES) m/z: 312.50 (M+1) (100%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customsolvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with saturated NaHCO3 solution (30 mL), water (30 mL), and brine (30 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customSolvent was evaporated
  7. customthe residue was purified by column chromatography (silica gel 230-400 mesh; 2-5% methanol in dichloromethane as eluent)

Sources & evidence

ORD record
ord-cb18bf13d7e64872b735b10d274aeb13
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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