p-Toluenesulfonic acid monohydrate → 2-(2-(2-Hydroxyethyl)-1H-indol-5-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591682Notes

Reaction equation

HRID 591682 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([CH:13]=O)=[CH:8][CH:7]=2.[NH2:15][C:16]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[C:17]=1[C:18]([NH2:20])=[O:19].S([O-])(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][C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([C:13]1[NH:20][C:18](=[O:19])[C:17]3[C:16](=[CH:24][C:23]([O:25][CH3:26])=[CH:22][C:21]=3[O:27][CH3:28])[N:15]=1)=[CH:8][CH:7]=2

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620292-(2-hydroxy-ethyl)-1H-indole-5-carbaldehyde

Product 1

HCID 1359390342-(2-(2-Hydroxyethyl)-1H-indol-5-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-(2-hydroxy-ethyl)-1H-indole-5-carbaldehyde (0.300 g, 1.58 mmol) and 2-amino-4,6-dimethoxy-benzamide (0.370 g, 1.90 mmol) in N,N-dimethylacetamide (5 mL) were added sodium hydrogen sulfite (58.5 wt %) (0.350 g, 1.90 mmol) and p-toluenesulfonic acid monohydrate (60 mg, 0.32 mmol). The reaction mixture was stirred at 120° C. for 16 hours under nitrogen and cooled to room temperature. The solvent was evaporated under reduced pressure. Water (20 mL) was added and the solid was separated by filtration, washed with water (30 mL) and dried under vacuum. Crude compound was purified by the Simpliflash system (5:20:75 methanol/ethyl acetate/CH2Cl2 as eluent) to give the title compound as an off-white solid. Yield: 0.22 g (38%). MP 237-238° C. 1H NMR (400 MHz, DMSO-d6): δ 11.83 (br s, 1H), 11.20 (s, 1H), 8.34 (s, 1H), 7.90 (d, J=8.2 Hz, 1H), 7.37 (d, J=8.6 Hz, 1H), 6.73 (d, J=1.9 Hz, 1H), 6.48 (d, J=1.9 Hz, 1H), 6.30 (s, 1H), 4.81 (t, J=5.1 Hz, 1H), 3.89 (s, 3H), 3.84 (s, 3H), 3.75 (q, J=6.63 Hz, 2H), 2.89 (t, J=7.0 Hz, 2H).

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. additionWater (20 mL) was added
  4. customthe solid was separated by filtration
  5. washwashed with water (30 mL)
  6. customdried under vacuum
  7. customCrude compound was purified by the Simpliflash system (5:20:75 methanol/ethyl acetate/CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-f2420849677545fb81bd9edcebdfdaa6
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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