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

HRID 591702Notes

Reaction equation

HRID 591702 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([CH:14]=O)=[CH:9][CH:8]=2)[CH3:3].[NH2:16][C:17]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[C:18]=1[C:19]([NH2:21])=[O:20].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:3][N:2]([CH2:4][C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([C:14]1[NH:21][C:19](=[O:20])[C:18]3[C:17](=[CH:25][C:24]([O:26][CH3:27])=[CH:23][C:22]=3[O:28][CH3:29])[N:16]=1)=[CH:9][CH:8]=2)[CH3:1]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620322-dimethylaminomethyl-1H-indole-5-carbaldehyde

Product 1

HCID 1359390422-(2-((Dimethylamino)methyl)-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-dimethylaminomethyl-1H-indole-5-carbaldehyde (0.88 g crude, 4.35 mmol) and 2-amino-4,6-dimethoxy-benzamide (0.85 g, 4.35 mmol) in N,N-dimethylacetamide (15 mL) were added sodium hydrogen sulfite (58.5 wt %, 0.95 g, 5.22 mmol) and p-toluenesulfonic acid (0.99 g, 5.22 mmol). The reaction mixture was stirred at 120° C. for 5 hours under nitrogen, then cooled to room temperature, and concentrated under reduced pressure. 30% aqueous sodium carbonate (50 mL) was then added. The separated solid was filtered, washed with water (50 mL), and dried under vacuum. Crude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 7 N ammonia in methanol 5% in CH2Cl2 as eluent) to give the title compound as an off-white solid. Yield: 0.83 g (50%). MP 187-188° C. 1H NMR (400 MHz, DMSO-d6): δ 11.82 (s, 1H), 11.34 (s, 1H), 8.38 (s, 1H), 7.93 (d, J=8.59 Hz, 1H), 7.40 (d, J=8.59 Hz, 1H), 6.73 (s, 1H), 6.49 (s, 1H), 6.40 (s, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.57 (s, 2H), 2.21 (s, 6H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. addition30% aqueous sodium carbonate (50 mL) was then added
  4. filtrationThe separated solid was filtered
  5. washwashed with water (50 mL)
  6. customdried under vacuum
  7. customCrude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 7 N ammonia in methanol 5% in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-e70bb02dfda941609b4523109f91e97b
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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