Hydrochloric Acid → n-{2-[n-(5-Chloro(2-pyridyl))carbamoyl]-4-methylphenyl}[4-(1-methyl(2-imidazolin-2-yl))phenyl]carboxamide

HRID 2362783Notes

Reaction equation

HRID 2362783 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=2[NH:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=2)=[O:20])=[O:10])=[N:6][CH:7]=1.Cl.[CH3:30][NH:31][CH2:32][CH2:33]N>CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=2[NH:18][C:19]([C:21]2[CH:22]=[CH:23][C:24]([C:27]3[N:31]([CH3:30])[CH2:32][CH2:33][N:28]=3)=[CH:25][CH:26]=2)=[O:20])=[O:10])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8014N-MethylethylenediamineHCID 22596418n-{2-[n-(5-Chloro(2-pyridyl))carbamoyl]-4-methylphenyl}(4-cyanophenyl)carboxamide

Product 1

HCID 10160926n-{2-[n-(5-Chloro(2-pyridyl))carbamoyl]-4-methylphenyl}[4-(1-methyl(2-imidazolin-2-yl))phenyl]carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the compound of N-(5-chloro(2-pyridyl))(5-methyl-2-nitrophenyl)carboxamide (1.48 g, 5.1 mmol) in methanol (10 ml) was added 5% Pt/C (1.48 g, 0.19 mmol). The mixture was applied hydrogen balloon at r.t. for 2 hrs. After the filtration by Celite, the filtrate was concentrated to give (2-aminophenyl)-N-(2-pyridyl)carboxamide, C, chloride, N (1.36 g, 100%). MS found for C13H12ClN3O M+=262, (M+2)+=264. Step 3: To a solution of the compound of (2-aminophenyl)-N-(2-pyridyl)carboxamide, C, chloride, N (1.36 g, 5.2 mmol) in dichloromethane (10 ml) was added 3-cyanobenzoly chloride (860 mg, 5.2 mmol) and pyridine (1.26 ml, 15.6 mmol). The mixture was stirred at r.t. overnight. After the evaporation of the solvent, the crude residue was purified by silica gel column chromatography using solvent system 25% ethyl acetate in hexane as eluent to give N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-methylphenyl}(4-cyanophenyl)carboxamide as a solid (830 mg, 41%). MS found for C21H15ClN4O2 M+=390, (M+2)+=392. Step 4: To a lotion of the compound of N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-methylphenyl}(4-cyanophenyl)carboxamide (830 mg, 2.1 mmol) in anhydrous methanol (5 ml) and ethyl acetate (10 ml) was saturated with hydrogen chloride gas at 0° C. The mixture was stirred at r.t. overnight. After the evaporated the solvent, the residue was dissolved in anhydrous methanol (5 ml) and N-methylethylenediamine (0.926 ml, 10.5 mmol) was added. The mixture was stirred under reflux condition for 2 hrs. After the evaporation of solvent, the crude residue was purified by RP-HPLC to give N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-methylphenyl}[4-(1-methyl(2-imidazolin-2-yl))phenyl]carboxamide as a white powder. MS found for C24H22ClN5O2 M+=448, (M+2)+=450.

Workup

  1. customAfter the evaporated the solvent
  2. dissolutionthe residue was dissolved in anhydrous methanol (5 ml)
  3. stirringThe mixture was stirred
  4. temperatureunder reflux condition for 2 hrs
  5. customAfter the evaporation of solvent
  6. customthe crude residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-2bb03f98c50a4d76811f39025eeb4efe
Source dataset
uspto-grants-2014_04
Patent number
US08691847B2

Reaction notes

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