Preparation method of 5-fluoro-2-methylsulfonyl-4-aminopyrimidine
A technology of methanesulfonyl pyrimidine and methanesulfonyl group, which is applied in the field of preparation of 5-fluoro-2-methanesulfonyl-4-aminopyrimidine, can solve unseen problems and the like, achieves convenient operation, and is beneficial to separation and purification , the effect of simple synthesis process
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Embodiment 1
[0019] This embodiment is a preparation method of 5-fluoro-2-methanesulfonyl-4-aminopyrimidine, according to the following reaction formula:
[0020]
[0021] The specific experimental process is as follows:
[0022] Using a three-necked flask, add 4.21g (0.02mol, 96%, 1eq) of newly prepared 4-chloro-5-fluoro-2-methanesulfonylpyrimidine, 20ml of tetrahydrofuran, and add ammonia water 3.09g (0.04mol , 25%, 2eq), after the completion of the dropwise reaction for 3 to 5 hours, the solvent THF was removed under reduced pressure after the reaction was completed, and 20 mL of water was added to the residue of the kettle. After cooling, a solid precipitated out, and a large amount of brown solid was obtained by filtration. After drying, it was recrystallized and columnar. Chromatography gave 2.48 g of brown solid product 5-fluoro-2-methylsulfonyl-4-aminopyrimidine, GC: 98%, yield 65%.
Embodiment 2
[0024] This embodiment is a preparation method of 5-fluoro-2-methanesulfonyl-4-aminopyrimidine, according to the following reaction formula:
[0025]
[0026] The specific experimental process is as follows:
[0027] Using a three-necked flask, add 4.21g (0.02mol, 96%, 1eq) of newly prepared 4-chloro-5-fluoro-2-methanesulfonylpyrimidine, 20ml of tetrahydrofuran, and add ammonia water 4.63g (0.06mol , 25%, 3eq), after the completion of the dropwise reaction for 3 to 5 hours, the solvent THF was removed under reduced pressure after the reaction was completed, and 20 mL of water was added to the residue of the kettle. After cooling, solids were precipitated, and a large amount of brown solids were obtained by filtration. After drying, they were recrystallized and columnar. Chromatography gave 2.79 g of brown solid product 5-fluoro-2-methanesulfonyl-4-aminopyrimidine, GC: 98%, yield 73%.
Embodiment 3
[0029] This example is the preparation method of 4-chloro-5-fluoro-2-methylsulfonyl pyrimidine, according to the following reaction formula:
[0030]
[0031] The specific experimental process is as follows:
[0032] Using a three-necked flask, add 4.21g (0.02mol, 96%, 1eq) of newly prepared 4-chloro-5-fluoro-2-methanesulfonylpyrimidine, 20ml of tetrahydrofuran, and add ammonia water 4.63g (0.06mol , 25%, 3eq), after the dropwise addition, react for 8-10h, remove the solvent tetrahydrofuran under reduced pressure after the reaction is completed, add 20mL water to the residue of the kettle, after cooling, solids are precipitated, and a large amount of brown solids are obtained by filtration, after drying, recrystallization and column Chromatography gave 3.06 g of brown solid product 5-fluoro-2-methanesulfonyl-4-aminopyrimidine, GC: 98%, yield 80%.
[0033] According to embodiment 1,2, increase the molar weight of ammoniacal liquor, the yield of product is promoted to 73% by...
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