4-Hydroxy-3-methylbenzaldehyde → HCID 136038014, compound

HRID 1498762Notes

Reaction equation

HRID 1498762 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[CH3:10].[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].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.O>CC(N(C)C)=O.CCOC(C)=O>[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]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:4][C:3]=1[CH3:10]

Participants

7

Reactant 4

HCID 1399014-Hydroxy-3-methylbenzaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 136038014HCID 136038014, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 4-hydroxy-3-methylbenzaldehyde (0.200 g, 1.47 mmol), 2-amino-4,6-dimethoxybenzamide (0.288 g, 1.47 mmol), NaHSO3 (94%, 0.163 g, 1.47 mmol), and p-TsOH.H2O (0.028 g, 0.147 mmol) in DMA (18.4 mL) was heated at reflux for 1 h. The mixture was diluted with EtOAc (300 mL), washed with saturated aqueous NH4Cl (2×150 mL) and brine (75 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The residue was triturated with MeOH and filtered off a yellow solid, which was freeze-dried from MeCN/H2O to provide 2-(4-hydroxy-3-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.161 g, 35%). Selected data: 1H NMR (300 MHz, DMSO-d6) δ 11.71 (s, 1H), 10.02 (s, 1H), 7.99 (d, J=1.88 Hz, 1H), 7.89 (dd, J=8.47, 2.29 Hz, 1H), 6.86 (d, J=8.50 Hz, 1H), 6.69 (d, J=2.31 Hz, 1H), 6.48 (d, J=2.31 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 2.18 (s, 3H); MS (APCI) m/z 313 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. washwashed with saturated aqueous NH4Cl (2×150 mL) and brine (75 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was triturated with MeOH
  8. filtrationfiltered off a yellow solid, which
  9. dry with materialwas freeze-dried from MeCN/H2O

Sources & evidence

ORD record
ord-d98bc70be0854e56b25b8150cb308edf
Source dataset
uspto-grants-2015_12
Patent number
US09199990B2

Reaction notes

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