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

HRID 591676Notes

Reaction equation

HRID 591676 reaction equation
[OH:1][CH2:2][C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH:12]=O)=[CH:7][CH:6]=2.[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].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:1][CH2:2][C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12]1[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]=1)=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 866620272-hydroxymethyl-1H-indole-5-carbaldehyde

Product 1

HCID 1359390332-(2-(Hydroxymethyl)-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-hydroxymethyl-1H-indole-5-carbaldehyde (90 mg, 0.51 mmol) and 2-amino-4,6-dimethoxy-benzamide (0.15 g, 0.77 mmol) in N,N-dimethylacetamide (5 mL) were added sodium hydrogen sulfite (58.5 wt %) (0.14 g, 0.77 mmol) and p-toluenesulfonic acid (20 mg, 0.10 mmol). The reaction mixture was stirred at 120° C. for 16 hours under nitrogen, cooled to room temperature, and concentrated under reduced pressure. Water (20 mL) was added. The separated solid was filtered, washed with water (20 mL) and ether (20 mL), and dried under vacuum. Crude compound was purified by column chromatography (silica gel 230-400 mesh; 0-5% methanol in CH2Cl2 as eluent), to give the title compound as an off-white solid. Yield: 0.06 g (33%). MP 264-265° C. 1H NMR (400 MHz, DMSO-d6): δ 11.85 (br s, 1H), 11.36 (s, 1H), 8.39 (s, 1H), 7.93 (dd, J=8.6 and 1.6 Hz, 1H), 7.44 (d, J=9.0 Hz, 1H), 6.73 (d, J=2.3 Hz, 1H), 6.49 (d, J=2.4 Hz, 1H), 6.41 (s, 1H). 5.34 (t, J=5.8 Hz, 1H), 4.63 (d, J=5.5 Hz, 2H), 3.90 (s, 3H), 3.85 (s, 3H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionWater (20 mL) was added
  4. filtrationThe separated solid was filtered
  5. washwashed with water (20 mL) and ether (20 mL)
  6. customdried under vacuum
  7. customCrude compound was purified by column chromatography (silica gel 230-400 mesh; 0-5% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-8daa21c350f94ea58518cddb0d1e1544
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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