p-Toluenesulfonic acid → 2-(2,6-Dimethylpyridin-4-yl)-6-(2-(pyrrolidin-1-yl)ethyl)quinazolin-4(3H)-one

HRID 591843Notes

Reaction equation

HRID 591843 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:18][C:19]1[CH:24]=[C:23]([CH:25]=O)[CH:22]=[C:21]([CH3:27])[N:20]=1.S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:18][C:19]1[CH:24]=[C:23]([C:25]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[CH2:17][CH2:16][CH2:15][CH2:14]4)[CH:7]=3)[N:1]=2)[CH:22]=[C:21]([CH3:27])[N:20]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 27630042,6-Dimethylpyridine-4-carbaldehydeHCID 23665763Sodium BisulfiteHCID 666709142-Amino-5-(2-pyrrolidin-1-yl-ethyl)-benzamide

Product 1

HCID 1363480312-(2,6-Dimethylpyridin-4-yl)-6-(2-(pyrrolidin-1-yl)ethyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-amino-5-(2-pyrrolidin-1-yl-ethyl)-benzamide (0.16 g, 0.69 mmol) in N,N-dimethyl acetamide (7 mL) under a nitrogen atmosphere was added 2,6-dimethyl-pyridine-4-carbaldehyde (0.09 g, 0.68 mmol), followed by sodium hydrogensulfite (0.14 g, 1.36 mmol) and p-toluenesulfonic acid (0.32 g, 1.7 mmol). The resulting mixture was heated at 120° C. overnight. Then, the solvent was removed under reduced pressure, the residue was diluted with ethyl acetate, and was extracted with water. The pH of the water layer was made basic by adding sodium bicarbonate, then the layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, and was evaporated under high vacuum. The crude yellow solid (0.09 g) was purified by column chromatography (silica gel 230-400 mesh; 95/5 methylene chloride/MeOH as eluent) to afford the title compound as a yellow solid. Yield: 54 mg (23%). MP 212.3-213.2° C. 1H NMR (400 MHz, CDCl3): δ 8.19 (s, 1H), 8.19 (br s, 1H), 7.83-7.77 (m, 1H), 7.76-7.70 (m, 3H), 3.0-3.15 (m, 2H), 2.78-2.88 (m, 2H), 2.7 (s, 6H), 2.58-2.68 (m, 4H), 1.8-1.95 (m, 4H). MS (ES+) m/z: 347.11 (M+1).

Workup

  1. customThen, the solvent was removed under reduced pressure
  2. additionthe residue was diluted with ethyl acetate
  3. extractionwas extracted with water
  4. additionby adding sodium bicarbonate
  5. extractionthe layer was extracted with methylene chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customwas evaporated under high vacuum
  8. customThe crude yellow solid (0.09 g) was purified by column chromatography (silica gel 230-400 mesh; 95/5 methylene chloride/MeOH as eluent)

Sources & evidence

ORD record
ord-8b408eeb38554ea59526bf77c68b3cf7
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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