Synthesis method of 4-bromo-1-methyl-1H-imidazole-5-carboxylic acid amide derivative
A technology of carboxylic acid amide and synthesis method, applied in the direction of organic chemistry, etc., can solve the problems of low yield, poor safety, poor reaction selectivity, etc.
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Embodiment 1
[0086]
[0087] Step 1. To 1-methyl-1H-imidazole-5-carboxylic acid (15g) (compound A-1) in N,N-dimethylformamide (150mL) solution, add 3-chloro-4-fluoro Aniline (21g) (compound A-2a), HATU (50g) and N,N-diisopropylethylamine (30g). The reaction solution was stirred at room temperature for 15 hours; after the reaction was completed, water (1000mL) was added to the reaction solution , stirred and filtered, the solid was washed with dichloromethane, filtered with suction, the filtrate was removed, and the solid was dried to obtain compound A-3a (25g, yield 83%);
[0088] Step 2. Add chloroform (100mL) solvent, N-bromosuccinimide (11g), and azobisisobutyronitrile (0.3g) to compound A-3a (4g), and stir the reaction solution at room temperature for 30 minutes The temperature was raised to 50° C. and stirred for 12 hours; after the reaction was completed, the solvent was concentrated and removed, and the residue was separated and purified by column chromatography to obtain compoun...
Embodiment 2
[0094]
[0095] Step 1. To 1-methyl-1H-imidazole-5-carboxylic acid (15g) (compound A-1) in N,N-dimethylformamide (225mL) solution, add cyclohexylamine (30g) in sequence ( Compound A-2b), HATU (60g) and triethylamine (45g). The reaction solution was stirred at room temperature for 12 hours; after the reaction was completed, water (1000mL) was added to the reaction solution, stirred and filtered, the solid was washed with dichloromethane, and Filter, remove the filtrate, and dry the solid to obtain compound A-3b (21g, yield 86%);
[0096] Step 2. Add chloroform (80mL) solvent, N-bromosuccinimide (12g), and azobisisobutyronitrile (0.26g) to compound A-3b (4g), and stir the reaction solution at room temperature for 30 minutes The temperature was raised to 60° C. and stirred for 12 hours; after the reaction was completed, the solvent was concentrated and removed, and the residue was separated and purified by column chromatography to obtain compound A-4b (5.4 g, yield 78%) as a p...
Embodiment 3
[0099]
[0100] Step 1. To 1-methyl-1H-imidazole-5-carboxylic acid (15g) (compound A-1) in DMA (180mL) solution, add tetrahydropyrrole (45g) (compound A-2c), HATU ( 45g) and N,N-diisopropylethylamine (37.5g). The reaction solution was stirred at room temperature for 10 hours; after the reaction was completed, water (1000mL) was added to the reaction solution, stirred and filtered, and the solid was washed with dichloromethane, pumped Filter, remove the filtrate, and dry the solid to obtain compound A-3c (17g, yield 80%);
[0101] Step 2. Add chloroform (88mL) solvent, N-bromosuccinimide (10g), and azobisisobutyronitrile (0.4g) to compound A-3c (4g), and stir the reaction solution at room temperature for 30 minutes The temperature was raised to 50° C. and stirred for 12 hours; after the reaction was completed, the solvent was concentrated and removed, and the residue was separated and purified by column chromatography to obtain solid compound A-4c (5 g, yield 68%);
[0102]...
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