Preparation method of 2-amino-5-bromopyridine

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-amino-5-bromopyridine. The method includes following reaction steps: taking 2-aminopyridine as a raw material and dichloromethane or trichloromethane as a solvent, and reacting with phenyl trimethyl ammonium tribromide at 20-50 DEG C for 1-3h, wherein a molar ratio of 2-aminopyridine to phenyl trimethyl ammonium tribromide is 0.7-1.4. The method has the advantages that generation of a lot of three-place byproducts in conventional preparation methods is avoided, and raw material waste and subsequent separation load are reduced; the raw material-2-aminopyridine is easy to get and low in cost, and the route is mild in reaction condition, high in yield and free of generation of the 3-place byproducts in the whole process and has industrialization prospect.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of 2-amino-5-pyridine. Background technique

[0002] Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, such as medicines, pesticides, dyes, surfactants, rubber additives, feed additives, food additives, adhesives, etc. Indispensable raw material in production. 2-Amino-5-bromopyridine is an important pharmaceutical intermediate that can be used to synthesize PI 3 Kinase inhibitors, halopyridine derivatives and thiazolylthiourea compounds, aminopyridine derivatives selective dopamine D 3 Receptor agonists, synthetic imidazo[1,2-a]pyridine compounds VEGFR-2 inhibitors and other drugs, also used in the treatment of autoimmune diseases, inflammatory diseases, cardiovas...

Examples

Embodiment 1

[0018] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condensing reflux tube into the three-necked flask , start stirring to make it evenly mixed, stir at 30°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with water 2-3 times, separate the layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, and obtain a crude product, recrystallize with benzene, filter, After drying, 10 g of yellow solid was obtained with a yield of 81%.

Embodiment 2

[0020] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condensing reflux tube into the three-necked flask , start stirring to make it evenly mixed, stir at 25°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with water 2-3 times, separate the layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, and obtain a crude product, recrystallize with benzene, filter, After drying, 8.43 g of yellow solid was obtained, with a yield of 78%.

[0021] This embodiment is the best implementation mode.

Embodiment 3

[0023] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g (0.1mol of phenyltrimethylammonium tribromide) and 300ml of dichloromethane into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condenser in the three-necked flask Return the tube, start stirring to make it evenly mixed, stir at 30°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with 20ml of water for 2-3 times, separate layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, obtain a crude product, recrystallize with benzene, After filtering and drying, 8.1 g of yellow solid was obtained, with a yield of 75%.

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of 2-amino-5-pyridine. Background technique

[0002] Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, such as medicines, pesticides, dyes, surfactants, rubber additives, feed additives, food additives, adhesives, etc. Indispensable raw material in production. 2-Amino-5-bromopyridine is an important pharmaceutical intermediate that can be used to synthesize PI 3 Kinase inhibitors, halopyridine derivatives and thiazolylthiourea compounds, aminopyridine derivatives selective dopamine D 3 Receptor agonists, synthetic imidazo[1,2-a]pyridine compounds VEGFR-2 inhibitors and other drugs, also used in the treatment of autoimmune diseases, inflammatory diseases, cardiovas...

Examples

Embodiment 1

[0018] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condensing reflux tube into the three-necked flask , start stirring to make it evenly mixed, stir at 30°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with water 2-3 times, separate the layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, and obtain a crude product, recrystallize with benzene, filter, After drying, 10 g of yellow solid was obtained with a yield of 81%.

Embodiment 2

[0020] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condensing reflux tube into the three-necked flask , start stirring to make it evenly mixed, stir at 25°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with water 2-3 times, separate the layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, and obtain a crude product, recrystallize with benzene, filter, After drying, 8.43 g of yellow solid was obtained, with a yield of 78%.

[0021] This embodiment is the best implementation mode.

Embodiment 3

[0023] Add 9.4g of 2-aminopyridine (0.1mol), 37.6g (0.1mol of phenyltrimethylammonium tribromide) and 300ml of dichloromethane into a 1L three-necked flask, insert a mechanical stirrer, a thermometer and a condenser in the three-necked flask Return the tube, start stirring to make it evenly mixed, stir at 30°C for 2 hours, wash with 40ml of saturated sodium chloride solution prepared in advance, the water phase is in the upper layer, and the organic phase is in the lower layer. Wash with 20ml of water for 2-3 times, separate layers, dry with anhydrous sodium sulfate, filter, and remove the solvent chloroform by rotary evaporation of the organic phase to obtain an oil, cool with ice water, add water to precipitate a solid, obtain a crude product, recrystallize with benzene, After filtering and drying, 8.1 g of yellow solid was obtained, with a yield of 75%.

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