p-Toluenesulfonic acid monohydrate → 2-(3-(2-Hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591847Notes

Reaction equation

HRID 591847 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S(=O)(O)[O-].[Na+]>CN(C)C(=O)C.C(=O)([O-])[O-].[K+].[K+]>[OH:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]([C:22]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)[CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 6453965Benzaldehyde, 3-(2-hydroxyethoxy)-HCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 1359390782-(3-(2-Hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 11430Potassium CarbonateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-amino-4,6-dimethoxy-benzamide (195 mg, 1.00 mmol), 3-(2-hydroxy-ethoxy)-benzaldehyde (166 mg, 1.00 mmol), p-toluenesulfonic acid monohydrate (38 mg, 0.20 mmol), and sodium bisulfite (264 mg, 1.50 mmol) in N,N-dimethylacetamide (10 mL) was stirred at 130° C. under nitrogen for 14 hours, cooled to room temperature, and diluted with 0.2 N potassium carbonate aqueous solution (50 mL). It was extracted with ethyl acetate (250 mL), dried over sodium sulfate, and concentrated. The solid residue was re-dissolved in dichloromethane (5 mL), and precipitated with ethyl acetate (15 mL) and hexanes (50 mL). It was filtered and washed with hexanes to afford the title compound as a yellow solid. Yield: 70 mg (20%). MP 244.8-246.0° C. 1H NMR (400 MHz, CDCl3): δ 7.64 (d, 1H), 7.60 (d, 1H), 7.45 (t, 1H), 7.12 (dd, 1H), 6.84 (d, 1H), 6.48 (d, 1H), 4.21 (t, 2H), 4.03 (t, 2H), 3.99 (s, 3H), 3.94 (s, 3H). MS (ES+) m/z: 343.55 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. extractionIt was extracted with ethyl acetate (250 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutionThe solid residue was re-dissolved in dichloromethane (5 mL)
  6. customprecipitated with ethyl acetate (15 mL) and hexanes (50 mL)
  7. filtrationIt was filtered
  8. washwashed with hexanes

Sources & evidence

ORD record
ord-cf7936962c9f4f8cb07b097620a9c039
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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