2-amino-N-(4-chlorophenyl)benzamide → 3-(4-chlorophenyl)-2-(6-(piperidin-1-yl)pyridin-3-yl)quinazolin-4(3H)-one

HRID 1846342Notes

Reaction equation

HRID 1846342 reaction equation
[NH2:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)=[O:5].[N:18]1([C:24]2[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][N:25]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>CCO>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:1]=[C:28]2[C:27]2[CH:26]=[N:25][C:24]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:31][CH:30]=2)=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 6704722-amino-N-(4-chlorophenyl)benzamideHCID 27639806-(Piperidin-1-yl)pyridine-3-carbaldehyde

Product 1

HCID 468417083-(4-chlorophenyl)-2-(6-(piperidin-1-yl)pyridin-3-yl)quinazolin-4(3H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-amino-N-(4-chlorophenyl)benzamide (0.318 g, 1.3 mmol) and 6-(piperidin-1-yl)nicotinaldehyde (1.3 mmol) were mixed in anhydrous EtOH (40 mL) and anhydrous CuCl2 (0.524 g, 3.9 mmol) was added. The reaction mixture was heated at reflux for 5 hours, cooled to room temperature, and stirred overnight. The reaction mixture was concentrated, diluted with ethyl acetate (150 mL), washed with water (2×100 mL), dried (MgSO4), filtered, and concentrated. Flash chromatograph on silica gel, eluting with 30% ethyl acetate/heptane to 75% ethyl acetate/heptane, afforded the title compound as a white solid (35%). 1H-NMR (300 MHz, DMSO-6): δ 8.16 (d, J=8.0 Hz, 1H), 8.11 (d, J=2.4 Hz, 1H), 7.86-7.91 (m, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.54-7.59 (m, 1H), 7.36-7.50 (m, 5H), 6.64 (d, J=9.0 Hz, 1H), 3.49-3.53 (m, 4H), 1.48-1.58 (m, 6H). MS (APCI) m/z: 417 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 hours
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with ethyl acetate (150 mL)
  5. washwashed with water (2×100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatograph on silica gel, eluting with 30% ethyl acetate/heptane to 75% ethyl acetate/heptane

Sources & evidence

ORD record
ord-fc3913ce70d04fc1a84126ddb4594298
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

Loading…