p-Toluenesulfonic acid → HCID 136038026, compound

HRID 555504Notes

Reaction equation

HRID 555504 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([O:13][CH3:14])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH:15]([C:17]1[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][C:23]([NH2:25])=[O:24])=[C:19]([CH3:29])[CH:18]=1)=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:8]1[CH:7]=[C:3]2[C:2](=[CH:10][C:9]=1[O:11][CH3:12])[N:1]=[C:15]([C:17]1[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][C:23]([NH2:25])=[O:24])=[C:19]([CH3:29])[CH:18]=1)[NH:6][C:4]2=[O:5]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 108672362-Amino-4,5-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 28825695HCID 28825695, compound

Product 1

HCID 136038026HCID 136038026, compoundYield 76.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-hydroxy-3,5-dimethoxybenzaldehyde (1.0 g, 6.66 mmol) in DMF (10 mL) was cooled to 0° C. under nitrogen. NaH (0.4 g, 10 mmol, 60% in oil) was added portion-wise. The reaction was stirred for 30 min, then 2-bromoacetamide (0.918 g, 6.66 mmol) was added and stirring was continued for 36 h at room temperature. The DMF was removed under reduced pressure and water (50 mL) was added. The mixture was extracted with EtOAc (50 mL×3). The combined organic layers were washed with an aqueous solution of NaOH (50 mL, 10%), washed with water (50 mL) and brine solution (50 mL) and dried over MgSO4 and concentrated to give 0.6 g of crude intermediate, which was purified by flash column chromatography to provide the desired intermediate (366 mg, 26%), as a white solid. A mixture of 2-amino-4,5-dimethoxybenzamide (0.2 g, 1.019 mmol), 2-(4-formyl-2,6-dimethyl-phenoxy acetamide (0.211 g, 1.019 mmol), sodium hydrogensulfite (0.116 g, 1.121 mmol) and p-toluenesulfonic acid (20 mg) in N,N-dimethyl acetamide (5 mL) was stirred at 150° C. for 16 h under nitrogen. The reaction mixture was cooled to room temperature and water (50 mL) was added. The white precipitate was filtered off and washed with cold water (30 mL×2) and dried under high vacuum to provide 2-(4-(6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetamide (300 mg, 76%) as a off white solid. Selected data: MS (ES) m/z: 384.1 (M+1); MP 354-356° C.

Workup

  1. filtrationThe white precipitate was filtered off
  2. washwashed with cold water (30 mL×2)
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-10d80e66694749a6a51c66543f5f22c3
Source dataset
uspto-grants-2011_11
Patent number
US08053440B2

Reaction notes

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