p-Toluenesulfonic acid → N-(1-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)piperidin-4-yl)benzamide

HRID 591622Notes

Reaction equation

HRID 591622 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=O.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:40][C:41]1[CH:49]=[C:48]([O:50][CH3:51])[CH:47]=[C:46]([O:52][CH3:53])[C:42]=1[C:43]([NH2:45])=[O:44]>CC(N(C)C)=O>[CH3:53][O:52][C:46]1[CH:47]=[C:48]([O:50][CH3:51])[CH:49]=[C:41]2[C:42]=1[C:43](=[O:44])[NH:45][C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]3[CH2:10][CH2:11][CH:12]([NH:15][C:16](=[O:23])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH2:13][CH2:14]3)=[CH:7][CH:8]=1)=[N:40]2

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86662018N-(1-(4-formylphenyl)piperidin-4-yl)benzamide

Product 1

HCID 135939097N-(1-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)piperidin-4-yl)benzamideYield 10%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of N-(1-(4-formylphenyl)piperidin-4-yl)benzamide (0.350 g, 1.10 mmol), NaHSO3 (0.180 g, 1.70 mmol) and p-TsOH (0.022 g, 0.11 mmol) and 2-amino-4,6-dimethoxybenzamide (0.223 g, 1.10 mmol) in DMA (10 mL) was heated at 150° C. overnight. The mixture was concentrated in vacuo, and the residue was dissolved in EtOAc and washed with H2O and brine, dried (Na2SO4), filtered and concentrated in vacuo. The resulting solid was purified by silica gel chromatography eluting with 10% to 50% CHCl3/MeOH/concentrated NH4OH in CH2Cl2 to afford the title compound (0.050 g, 10%): 1H NMR (300 MHz, DMSO-d6): δ 11.75 (s, 1H), 8.26 (d, J=7.4 Hz, 1H), 8.10 (d, J=9.0 Hz, 2H), 7.83 (d, J=6.9 Hz, 2H), 7.44-7.49 (m, 3H), 7.05 (d, J=8.8 Hz, 2H), 6.68 (s, 1H), 6.46 (s, 1H), 3.93-4.17 (m, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 2.91-3.08 (m, 2H), 1.82-1.93 (m, 2H), 1.52-1.72 (m, 2H); APCI MS m/z 485 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting solid was purified by silica gel chromatography
  8. washeluting with 10% to 50% CHCl3/MeOH/concentrated NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-2c24f666033d4955a2de8617655326ba
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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