Acetic Acid → 2-(4-hydroxy-3-(2-hydroxyethyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 336749Notes

Reaction equation

HRID 336749 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)[CH:7]=[CH:8][C:9]=1[O:10]COC.C(O)(=O)C.S(=O)(=O)(O)O>O>[OH:10][C:9]1[CH:8]=[CH:7][C:6]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][C:18]([O:27][CH3:28])=[CH:19][C:20]=3[O:25][CH3:26])[N:15]=2)=[CH:5][C:4]=1[CH2:3][CH2:2][OH:1]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 1363988462-[3-(2-hydroxy-ethyl)-4-methoxymethoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one

Product 1

HCID 1360380072-(4-hydroxy-3-(2-hydroxyethyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-oneYield 21.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-amino-4,6-dimethoxy-benzamide (0.25 g, 1.27 mmol), 3-(2-hydroxy-ethyl)-4-methoxymethoxy-benzaldehyde (0.268 g, 1.27 mmol), sodium hydrogensulfite (0.146 g, 1:4 mmol) and p-toluenesulfonic acid (0.025 g, 0.127 mmol) in N,N-dimethyl acetamide (8 mL) was stirred at 150° C. overnight under nitrogen atmosphere. The reaction mixture was cooled to room temperature, the solvent evaporated under reduced pressure. Water (70 mL) was added to obtain a solid. The yellow solid was filtered off, washed with water and dried under vacuum to provide crude 2-[3-(2-hydroxy-ethyl)-4-methoxymethoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.182 g, 36.7%) which was used as such in the next step. A solution of 2-[3-(2-hydroxy-ethyl)-4-methoxymethoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.18 g), 50% acetic acid solution (4 mL) and catalytic amount of concentrated sulfuric acid (0.02 mL) was heated at 70° C. for 2.5 h. After cooling to room temperature the reaction mixture was diluted with water (30 mL) to obtain a solid. The solid was filtered off, washed with water and dried under high vacuum to provide crude solid (0.135 g, 85%). The crude was purified by flash column chromatography to give pure 2-(4-hydroxy-3-(2-hydroxyethyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.035 g. 8% over 2 steps). Selected data: MS (ES) m/z: 343.0; MP 249-250.3° C.

Workup

  1. customto obtain a solid
  2. filtrationThe solid was filtered off
  3. washwashed with water
  4. customdried under high vacuum
  5. customto provide crude solid (0.135 g, 85%)
  6. customThe crude was purified by flash column chromatography

Sources & evidence

ORD record
ord-1abff59be8c44686bf70e6d4ccf50714
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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