p-Toluenesulfonic acid → 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one

HRID 336757Notes

Reaction equation

HRID 336757 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[C:3]=1[C:4]([NH2:6])=[O:5].C([Si](C)(C)[O:18][CH2:19][CH2:20][O:21][C:22]1[C:29]([CH3:30])=[CH:28][C:25]([CH:26]=O)=[CH:24][C:23]=1[CH3:31])(C)(C)C.S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C)C(=O)C.O.C1COCC1.CO>[OH:18][CH2:19][CH2:20][O:21][C:22]1[C:29]([CH3:30])=[CH:28][C:25]([C:26]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][C:7]=3[CH3:12])[N:1]=2)=[CH:24][C:23]=1[CH3:31]

Participants

10

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 2724141Tetrabutylammonium FluorideHCID 23665763Sodium BisulfiteHCID 666613962-Amino-4,6-dimethylbenzamideHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 1359079412-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-oneYield 24%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
155 °C

Procedure

A mixture of 2-amino-4,6-dimethyl benzamide (0.2 g, 1.22 mmol), 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,5-dimethyl-benzaldehyde (0.376 g, 1.22 mmol), sodium hydrogensulfite (0.22 g, 1.22 mmol) and p-toluenesulfonic acid (0.116 g, 0.61 mmol) in N,N-dimethyl acetamide (10 mL) was stirred at 155° C. for 14 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL). The solid crashed out and was collected by filtration to afford impure product. The solid was re-dissolved in THF (30 mL) and mixed with TBAF in THF (5 mL, 5 mmol). The reaction mixture was stirred at room temperature for 14 h and concentrated using a rotary evaporator to afford an oily residue. Further purification by column (SiO2, EtOAc/DCM/MeOH=12:4:1) yielded an off-white solid. This solid was diluted with MeOH (10 mL) to make a slurry. The solid was collected by filtration and washed with MeOH to afford 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one (98 mg, 24%) as a white solid. Selected data: MS (ES) m/z: 339.10; MP 259.6-261.2° C.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationwas collected by filtration
  3. customto afford impure product
  4. stirringThe reaction mixture was stirred at room temperature for 14 h
  5. concentrationconcentrated
  6. customa rotary evaporator
  7. customto afford an oily residue
  8. customFurther purification by column (SiO2, EtOAc/DCM/MeOH=12:4:1)
  9. customyielded an off-white solid
  10. filtrationThe solid was collected by filtration
  11. washwashed with MeOH

Sources & evidence

ORD record
ord-fca64323ecc1480b88e0a0676f59582a
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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