p-Toluenesulfonic acid monohydrate → 2-[4-(2-hydroxy-ethoxy)-3-methyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one

HRID 591731Notes

Reaction equation

[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][C:6]=1[CH3:13].[NH2:14][C:15]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[C:16]=1[C:17]([NH2:19])=[O:18].OS([O-])=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]2[NH:19][C:17](=[O:18])[C:16]3[C:15](=[CH:23][C:22]([O:24][CH3:25])=[CH:21][C:20]=3[O:26][CH3:27])[N:14]=2)=[CH:7][C:6]=1[CH3:13]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 4-(2-hydroxy-ethoxy)-3-methylbenzaldehyde (1.46 g, 8.08 mmol) and 2-amino-4,6-dimethoxybenzamide (1.58 g, 8.08 mmol) in N,N-dimethylacetamide (20 mL) were added NaHSO3 (58.5 wt %, 2.20 g, 12.12 mmol) and p-toluenesulfonic acid monohydrate (0.38 g, 2.02 mmol). The reaction mixture was stirred at 110° C. for 16 hours, then cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure. The residue was triturated with water (50 mL). The resulting slurry was filtered and solid was washed with water, ether, and hexanes to obtain 2-[4-(2-hydroxy-ethoxy)-3-methyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one as a beige solid. Yield: 2.75 g (95%).

Workup

temperaturecooled to room temperature
customN,N-dimethylacetamide was removed under reduced pressure
customThe residue was triturated with water (50 mL)
filtrationThe resulting slurry was filtered
washsolid was washed with water, ether, and hexanes

Sources & evidence

ORD record: ord-b05c06128eba40548aa06b148ee72d3f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238640B2

Reaction notes

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