p-Toluenesulfonic acid → 3-(4-sec-butylphenyl)-2-(6-methoxypyridin-3-yl)quinazolin-4(3H)-one

HRID 1846336Notes

Reaction equation

HRID 1846336 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH:9]=O)=[CH:5][CH:4]=1.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:27][C:28]1[CH:46]=[CH:45][CH:44]=[CH:43][C:29]=1[C:30]([NH:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([CH2:41][CH3:42])[CH3:40])=[CH:35][CH:34]=1)=[O:31]>CC(N(C)C)=O>[CH:39]([C:36]1[CH:37]=[CH:38][C:33]([N:32]2[C:30](=[O:31])[C:29]3[C:28](=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:27]=[C:9]2[C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:34][CH:35]=1)([CH2:41][CH3:42])[CH3:40]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 33645766-Methoxypyridine-3-carbaldehydeHCID 167700372-Amino-N-(4-sec-butylphenyl)benzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 468414133-(4-sec-butylphenyl)-2-(6-methoxypyridin-3-yl)quinazolin-4(3H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

6-Methoxy-3-pyridinecarboxaldehyde (1.20 mmol), NaHSO3 (0.200 g, 1.90 mmol) and p-TsOH (0.024 g, 0.12 mmol) were added to a solution of 2-amino-N-(4-sec-butylphenyl)benzamide (0.340 g, 1.20 mmol) in DMA (10 mL). The mixture was heated and stirred at 150° C. overnight and concentrated in vacuo. The residue was dissolved in EtOAc, and washed with H2O, then brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 15% to 100% EtOAc in heptane, afforded the title compound as a white solid (26%). 1H-NMR (300 MHz, DMSO-d6): δ 8.11-8.27 (m, 2H), 7.89-7.91 (m, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.51-7.67 (m, 2H), 7.11-7.33 (m, 4H), 6.62 (d, J=8.0 Hz, 1H), 3.77 (s, 3H), 2.54-2.68 (m, 1H), 1.30-1.71 (m, 2H), 1.16 (d, J=7.0 Hz, 3H), 0.64 (t, J=7.4 Hz, 3H). MS (APCI) m/z: 386 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with H2O
  5. dry with materialbrine, dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel
  9. washeluting with 15% to 100% EtOAc in heptane

Sources & evidence

ORD record
ord-59d627152e774058b7abf294dba2b145
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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