p-Toluenesulfonic acid → 3-(4-fluorophenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

HRID 1846279Notes

Reaction equation

HRID 1846279 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[C:12]([CH3:13])=[CH:11][C:8]([CH:9]=O)=[CH:7][C:6]=1[CH3:14].[NH2:15][C:16]1[CH:31]=[CH:30][CH:29]=[CH:28][C:17]=1[C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:19].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C.O>[F:27][C:24]1[CH:25]=[CH:26][C:21]([N:20]2[C:18](=[O:19])[C:17]3[C:16](=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:15]=[C:9]2[C:8]2[CH:11]=[C:12]([CH3:13])[C:5]([O:4][CH2:3][CH2:2][OH:1])=[C:6]([CH3:14])[CH:7]=2)=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 4788222-amino-N-(4-fluorophenyl)benzamideHCID 23665763Sodium BisulfiteHCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 468407373-(4-fluorophenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
155 °C

Procedure

To a mixture of 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (0.420 g, 2.17 mmol) and 2-amino-N-(4-fluoro-phenyl)-benzamide (0.500 g, 2.17 mmol) in N,N-dimethylacetamide (5 mL) was added sodium hydrogen sulfite (0.350 g, 3.26 mmol) and p-toluenesulfonic acid (0.21 g, 0.11 mmol). The reaction mixture was heated at 155° C. for 14 hours. The reaction mixture was cooled to room temperature and diluted with cold water (20 mL) to produce the precipitate. The yellow solid was filtered, washed with cold water (2×20 mL), methanol, and dried under vacuum to provide crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent) to give the title compound as white solid. Yield: 0.10 g (11%). MP 95-97° C. 1H-NMR (400 MHz, CDCl3): δ 8.35 (d, 1H), 7.81-7.78 (d, 2H), 7.58-7.40 (m, 1H), 7.20-7.15 (m, 2H), 7.15-7.01 (m, 4H), 3.98-3.80 (m, 4H), 2.21 (s, 6H), 2.01 (t, 1H). MS (ES+) m/z: 405.01 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customto produce the precipitate
  3. filtrationThe yellow solid was filtered
  4. washwashed with cold water (2×20 mL), methanol
  5. customdried under vacuum
  6. customto provide crude product, which
  7. customwas purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent)

Sources & evidence

ORD record
ord-4af102d05314497ea62406130d9ca81f
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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