p-Toluenesulfonic acid → 2-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethylquinazolin-4(3H)-one

HRID 591781Notes

Reaction equation

HRID 591781 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[C:3]=1[C:4]([NH2:6])=[O:5].[CH3:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH3:30])[C:21]=1[O:22][CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[CH:17]=O.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:30][C:20]1[CH:19]=[C:16]([C:17]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][C:7]=3[CH3:12])[N:1]=2)[CH:15]=[C:14]([CH3:13])[C:21]=1[O:22][CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 23665763Sodium BisulfiteHCID 289325703,5-Dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehydeHCID 666613962-Amino-4,6-dimethylbenzamide

Product 1

HCID 1363479982-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethylquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-amino-4,6-dimethyl-benzamide (0.20 g, 1.22 mmol) and 3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde (0.36 g, 1.46 mmol) in N,N-dimethylacetamide (10 mL) was added NaHSO3 (58.5 wt %, 0.55 g, 3.05 mmol) and p-TSA (0.46 g, 2.44 mmol). The reaction mixture was heated to 110° C. for 2 hours, then cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure, the residue was diluted with sodium bicarbonate solution (50 mL), and the solid separated was filtered and dried under vacuum. The crude compound was purified by column chromatography (silica gel 230-400 mesh; 6% methanol in dichloromethane as eluent) to give the title compound as a white solid. Yield: 0.145 g (30%). MP 181-182° C. 1H NMR (400 MHz, DMSO-d6): δ 10.62 (s, 1H), 7.75 (s, 2H), 7.44 (s, 1H), 7.03 (s, 1H), 3.95 (t, J=6.0 Hz, 2H), 2.94 (t, J=6.0 Hz, 2H), 2.85 (s, 3H), 2.65 (s, 4H), 2.44 (s, 3H), 2.39 (s, 6H), 1.84 (s, 4H). MS (ES+) m/z: 392.13 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. customN,N-dimethylacetamide was removed under reduced pressure
  3. additionthe residue was diluted with sodium bicarbonate solution (50 mL)
  4. customthe solid separated
  5. filtrationwas filtered
  6. customdried under vacuum
  7. customThe crude compound was purified by column chromatography (silica gel 230-400 mesh; 6% methanol in dichloromethane as eluent)

Sources & evidence

ORD record
ord-9c36fa1912a1414087a7c1dbc8d6942e
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…