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

HRID 591816Notes

Reaction equation

HRID 591816 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]=O)[CH:5]=[C:4]([CH3:10])[N:3]=1.[NH2:11][C:12]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)=[CH:17][C:13]=1[C:14]([NH2:16])=[O:15].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:16][C:14](=[O:15])[C:13]3[C:12](=[CH:20][CH:19]=[C:18]([CH2:21][N:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)[CH:17]=3)[N:11]=2)[CH:5]=[C:4]([CH3:10])[N:3]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 27630042,6-Dimethylpyridine-4-carbaldehydeHCID 23665763Sodium BisulfiteHCID 666710512-Amino-5-(4-methyl-piperazin-1-ylmethyl)benzamide

Product 1

HCID 1359390682-(2,6-Dimethylpyridin-4-yl)-6-((4-methylpiperazin-1-yl)methyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 2,6-dimethylpyridine-4-carbaldehyde (0.14 g, 1.00 mmol) in N,N-dimethyl acetamide (8 mL) were added 2-amino-5-(4-methyl-piperazin-1-ylmethyl)benzamide (0.25 g, 1.00 mmol), sodium hydrogensulfite (0.18 g, 1.20 mmol), and p-toluenesulfonic acid (0.057 g, 0.30 mmol). The reaction mixture was stirred at 115° C. for 20 hours under nitrogen, then cooled to room temperature. Solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane, washed with sat. NaHCO3, water, then brine, and dried over anhydrous sodium sulfate. Solvent was evaporated and the residue was purified by column chromatography (silica gel 230-400 mesh; 2-3% 7 M ammonia in methanol and dichloromethane as eluent) to give the title compound. Yield: 0.035 g (9.6%). MP 229-230° C. 1H NMR (400 MHz, CDCl3): δ 8.30 (br s, 1H), 7.88 (s, 2H), 7.84 (m, 2H), 3.66 (s, 2H), 2.72 (s, 6H), 2.50 (br s, 8H), 2.30 (s, 3H). MS (ES) m/z: 364.17 (M+1), 182.67 (100%).

Workup

  1. temperaturecooled to room temperature
  2. customSolvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with sat. NaHCO3, water
  5. dry with materialbrine, and dried over anhydrous sodium sulfate
  6. customSolvent was evaporated
  7. customthe residue was purified by column chromatography (silica gel 230-400 mesh; 2-3% 7 M ammonia in methanol and dichloromethane as eluent)

Sources & evidence

ORD record
ord-1a3fa5b7e02843fda1963e6c74970a13
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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