p-Toluenesulfonic acid → 5,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-one

HRID 1498656Notes

Reaction equation

HRID 1498656 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH:21]=O.S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C.O>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:21]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][N:15]=1)=[N:1]2

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 142732-PyridinecarboxaldehydeHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 1360379985,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-oneYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-amino-4,6-dimethoxybenzamide (0.15 g, 0.764 mmol) in N,N-dimethyl acetamide (5 mL) were added 2-pyridine carboxaldehyde (0.082 g, 0.764 mmol), sodium hydrogen sulphite (58.5%, 0.15 g, 0.84 mmol), and p-toluenesulfonic acid (15 mg, 0.0764 mmol). The reaction mixture was stirred at 150° C. overnight. The mixture was cooled to room temperature. Water (40 mL) was added and the reaction mixture was extracted with dichloromethane (2×50 mL). The combined organic layers were washed with water and dried over anhydrous Na2SO4. The solvent was removed and the crude compound was purified by column chromatography (silica gel 230-400 mesh; 1% methanol in CH2Cl2 as eluent) to give 5,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-one (0.077 g, 36%) as a white solid. 5,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-one was converted to the corresponding hydrochloride. Selected data: MS (m/z): 284.0; MP 215-217° C. (hydrochloride).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionthe reaction mixture was extracted with dichloromethane (2×50 mL)
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe solvent was removed
  6. customthe crude compound was purified by column chromatography (silica gel 230-400 mesh; 1% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-ce70bbb501914a08bfda7b3b04b8dd25
Source dataset
uspto-grants-2015_12
Patent number
US09199990B2

Reaction notes

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