p-Toluenesulfonic acid → HCID 135939076, compound

HRID 591832Notes

Reaction equation

HRID 591832 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:19][C:20]1[CH:25]=[C:24]([CH:26]=O)[CH:23]=[C:22]([CH3:28])[N:21]=1.S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:19][C:20]1[CH:25]=[C:24]([C:26]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][CH:9]=[C:8]([CH2:11][CH2:12][N:13]4[CH2:14][CH2:15][O:16][CH2:17][CH2:18]4)[CH:7]=3)[N:1]=2)[CH:23]=[C:22]([CH3:28])[N:21]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 27630042,6-Dimethylpyridine-4-carbaldehydeHCID 23665763Sodium BisulfiteHCID 66670900HCID 66670900, compound

Product 1

HCID 135939076HCID 135939076, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-amino-5-(2-morpholin-4-yl-ethyl)-benzamide (0.18 g, 0.70 mmol) in N,N-dimethyl acetamide (7 mL) under nitrogen atmosphere were added 2,6-dimethyl-pyridine-4-carbaldehyde (0.10 g, 0.70 mmol), sodium hydrogensulfite (58.5 wt %, 0.15 g, 1.40 mmol) and p-toluenesulfonic acid (0.34 g, 1.80 mmol). The resulting mixture was heated at 120° C. for 16 hours, then cooled to room temperature. The solvent was removed under reduced pressure, and the residue was diluted with methylene chloride (100 mL). The organic phase was washed with saturated aqueous sodium bicarbonate solution, then water, and dried over anhydrous sodium sulfate. The crude orange solid (0.21 g) was purified by column chromatography (silica gel 230-400 mesh; 95:5 methylene chloride and MeOH as eluent) to give the title compound as a yellow solid. Yield: 0.11 g (42%). MP 248.5-249.3° C. 1H NMR (400 MHz, CDCl3): δ 11.6 (s, 1H), 8.18 (s, 1H), 7.87-7.76 (m, 3H), 7.76-7.65 (m, 1H), 3.76 (t, J=4.49 Hz, 4H), 2.99 (t, J=8.01 Hz, 4H), 2.71 (s, 6H), 2.75-2.65 (m, 2H), 2.56 (br s, 4H). MS (ES+) m/z: 363.16 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under reduced pressure
  3. additionthe residue was diluted with methylene chloride (100 mL)
  4. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution
  5. dry with materialwater, and dried over anhydrous sodium sulfate
  6. customThe crude orange solid (0.21 g) was purified by column chromatography (silica gel 230-400 mesh; 95:5 methylene chloride and MeOH as eluent)

Sources & evidence

ORD record
ord-07dac98f9ee7479284cef8cc22d19a13
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…