* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 5 h; Stage #2: With ammonia In methanol at 20℃;
To a solution of 1-methyl-1H-imidazole-4-carboxylic acid (1 g, 7.94 mmol) in DCM (10 mL) was added (COd)2 (2 g, 15.9 mmol) and DIVIF (2 drops). After stirred at room temperature for 5 hrs, the reaction mixture was evaporated in vacuum. The residue was then dissloved in 7 N NH3 in MeOH (10 mL). After stirred at room temperature overnight, the reaction mixture was evaporated in vacuum. The residue was purified by flash column chromatograph (ACN in water, 5percent to 60percent) to afford 1-methyl-1H-imidazole-4-carboxylic acid amide (480 mg, 48percent) as a white solid. ‘H NIVIR (400 IVIHz, DMSO-d6): ö = 7.62 (d, J= 11.6Hz, 2H), 7.24 (s, 1H), 7.03 (s, 1H), 3.68 (s, 3H).
Reference:
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1990, vol. 26, # 4, p. 407 - 409[2] Khimiya Geterotsiklicheskikh Soedinenii, 1990, # 4, p. 475 - 477
C-(1-methyl-1H-imidazol-4-yl)methylamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 24.0h;Heating / reflux;
[0519] To a solution of <strong>[129993-47-1]1-methyl-1H-imidazole-4-carboxylic acid amide</strong> (0.80 g, 6.4 mmol) in THF (15 ml) at 0 C. was added LiAlH4 (486 mg, 12.8 mmol). The mixture was refluxed for 24 h, cooled to 0 C., then carefully quenched with sat NaHCO3 (2 ml), diluted with ether (80 ml), and filtered through a pad of Celite. The filtrate was dried over Na2SO4 and concentrated to give 476 mg of yellow oil in 67% yield and was used without any further purification. [0520] 1H NMR (CDCl3): delta 7.35 (s, 1H), 6.73 (s, 1H), 3.78 (s, 2H), 3.64 (s, 3H).
With lithium aluminium tetrahydride; In tetrahydrofuran;Reflux;
To a solution of <strong>[129993-47-1]1-methyl-1H-imidazole-4-carboxylic acid amide</strong> (480 mg, 3.84 mmol) in THF (30 mL) was added LiA1H4 (584 mg, 15.4 mmol). After stirred at reflux overnight, the reaction was quenched by H20 (2 mL). Then the mixture was dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated in vacuum to afford C-(1-methyl-1H-imidazol-4-yl)- methylamine as a crude product which was used for next step without further purification.
In dichloromethane; acetonitrile; for 18.0h;Reflux;
Preparation of intermediate II-33; A mixture of 1-Methyl-1 H-imidazole-4-carboxamide, (cas: 129993-47-1 ) (560 mg, 4.47 mmol, 1 eq) and 2-bromo-3'-methoxyacetophenone (1.124 g, 4.91 mmol, 1.1 eq) in MeCN (10 mL) and DMF (3 mL) was refluxed for 18 h. On cooling to 0C, the resulting solid was filtered off, washed with MeCN and dried to give 6-(3- methoxy-phenyl)-2-methyl-8-oxo-7,8-dihydro-imidazo[1 ,5-a]pyrazin-2-ium;bromide, intermediate II-33, (796 mg, 53% yield) as a white solid.
With 1-hydroxy-1H-benzotriazol hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 20℃;
General procedure: To a solution of 1-methyl-1Himidazole-4-carboxylic acid (0.50 g, 4.0 mmol), 1-hydroxybenztriazole monohydrate (0.74 g, 4.8 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) in acetonitrile (10 mL) was added a solution of 3-(trifluoromethoxy) benzylamine 8(0.84 g, 4.4 mmol) in acetonitrile (10 mL), and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated in vacuo, and saturated aqueous NaHCO3solution was added to the residue. After extraction with ethyl acetate, the organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (0-10% MeOH in CHCl3) to obtain 9(1.18 g, 98%) as a colorless powder
With 1-hydroxy-1H-benzotriazol hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 20℃;
General procedure: To a solution of 1-methyl-1Himidazole-4-carboxylic acid (0.50 g, 4.0 mmol), 1-hydroxybenztriazole monohydrate (0.74 g, 4.8 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) in acetonitrile (10 mL) was added a solution of 3-(trifluoromethoxy) benzylamine 8(0.84 g, 4.4 mmol) in acetonitrile (10 mL), and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated in vacuo, and saturated aqueous NaHCO3solution was added to the residue. After extraction with ethyl acetate, the organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (0-10% MeOH in CHCl3) to obtain 9(1.18 g, 98%) as a colorless powder
To a solution of <strong>[41716-18-1]1-<strong>[41716-18-1]methyl-1H-imidazole-4-carboxylic acid</strong></strong> (1 g, 7.94 mmol) in DCM (10 mL) was added (COd)2 (2 g, 15.9 mmol) and DIVIF (2 drops). After stirred at room temperature for 5 hrs, the reaction mixture was evaporated in vacuum. The residue was then dissloved in 7 N NH3 in MeOH (10 mL). After stirred at room temperature overnight, the reaction mixture was evaporated in vacuum. The residue was purified by flash column chromatograph (ACN in water, 5percent to 60percent) to afford <strong>[41716-18-1]1-<strong>[41716-18-1]methyl-1H-imidazole-4-carboxylic acid</strong></strong> amide (480 mg, 48percent) as a white solid. ?H NIVIR (400 IVIHz, DMSO-d6): oe = 7.62 (d, J= 11.6Hz, 2H), 7.24 (s, 1H), 7.03 (s, 1H), 3.68 (s, 3H).