p-Toluenesulfonic acid → 2-(4-(1-Acetylpiperidin-4-yloxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 591711Notes

Reaction equation

HRID 591711 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[C:15]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][CH:26]=2)[CH2:20][CH2:19]1)(=[O:17])[CH3:16].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[C:15]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:26]=[CH:27][C:28]([C:29]3[NH:6][C:4](=[O:5])[C:3]4[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=4[O:13][CH3:14])[N:1]=3)=[CH:31][CH:32]=2)[CH2:20][CH2:19]1)(=[O:17])[CH3:16]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 230875244-(1-Acetylpiperidin-4-yloxy)benzaldehydeHCID 23665763Sodium Bisulfite

Product 1

HCID 1359390502-(4-(1-Acetylpiperidin-4-yloxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 2-amino-4,6-dimethoxy-benzamide (0.20 g, 1.0 mmol) and 4-(1-acetyl-piperidin-4-yloxy)-benzaldehyde (0.25 g, 1.0 mmol) in N,N-dimethyl acetamide (5 mL), NaHSO3 (0.20 g, 1.1 mmol) and p-TSA (20 mg, 0.10 mmol) were added and the reaction mixture was heated at 115° C. for 16 hours. The reaction mixture was cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure. The residue was diluted with water and the solid was collected; the crude product was purified by column chromatography on silica gel (230-400 mesh), using 5% methanol in CH2Cl2 as eluent, to give the title compound. Yield: 0.2 g (47%). MP 275-277° C. 1H NMR (400 Hz, CDCl3): δ 11.94 (s, 1H), 8.16 (d, 2H), 7.10 (d, 2H), 6.70 (d, 1H), 6.50 (d, 1H), 4.76 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.70 (m, 1H), 3.30 (m, 2H), 3.20 (m, 1H), 2.04 (s, 3H), 1.95 (m, 2H), 1.64 (m, 1H), 1.52 (m, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customN,N-dimethylacetamide was removed under reduced pressure
  3. additionThe residue was diluted with water
  4. customthe solid was collected
  5. customthe crude product was purified by column chromatography on silica gel (230-400 mesh)

Sources & evidence

ORD record
ord-d32aacb8eb73419bba1aec23bae6cdd8
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…