Preparation method of 2-amido methylpyrimidine hydrochloride

Abstract

The invention discloses a preparation method of 2-amido methylpyrimidine hydrochloride, and relates to the technical field of organic synthesis. The preparation method comprises the steps that 2-amido methylpyrimidine mesylate is taken as a raw material, sodium methylate is added at certain temperature, suction filtration is conducted after reacting is finished, the temperature of filtrate is decreased to certain temperature, an enough amount of hydrochloric acid gas is introduced, and stirring and filtering are conducted to obtain the product 2-amido methylpyrimidine hydrochloride. The 2-amido methylpyrimidine hydrochloride is simple in preparation technology, low in cost and simple in aftertreatment; in addition, the product purity reaches 99.5% or above, the yield reaches 85% or above, and the preparation method is suitable for industrialized production.

Description

Technical field:

[0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-aminomethylpyrimidine hydrochloride. Background technique:

[0002] 2-Aminomethylpyrimidine hydrochloride, CAS No. 372118-67-7, is the raw material of the drug Avanafil, Avanafil, CAS No.: 330784-47-9, Chinese alias: 4-[(3 -Chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinylmethyl)-5-pyrimidinemethanesulfonamide, is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) in men.

[0003] WO2005 / 113553 uses 2-cyanopyrimidine as a raw material, under the conditions of methanol, water and hydrogen chloride, and palladium carbon catalytic hydrogenation method to prepare 2-aminomethylpyrimidine hydrochloride; US2004 / 142930 uses 2-cyanopyrimidine Pyrimidine is used as a raw material, and 2-aminomethylpyrimidine hydrochloride is prepared by nickel-catalyzed hydrogenation under ...

Examples

Embodiment 1

[0014] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to -10°C, add solid sodium methoxide in batches, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to -10°C, pass through A sufficient amount of hydrochloric acid gas was reacted for 2 hours, suction filtered and dried to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 89%.

Embodiment 2

[0016] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to -10°C, add sodium methoxide / methanol liquid dropwise, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to -10°C, pass Add sufficient amount of hydrochloric acid gas, react for 2 hours, suction filter, and dry to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 86%.

Embodiment 3

[0018] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to 0°C, add solid sodium methoxide in batches, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to 0°C, and inject enough hydrochloric acid gas, reacted for 2 hours, suction filtered and dried to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 88.5%.

Technical field:

[0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-aminomethylpyrimidine hydrochloride. Background technique:

[0002] 2-Aminomethylpyrimidine hydrochloride, CAS No. 372118-67-7, is the raw material of the drug Avanafil, Avanafil, CAS No.: 330784-47-9, Chinese alias: 4-[(3 -Chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinylmethyl)-5-pyrimidinemethanesulfonamide, is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) in men.

[0003] WO2005 / 113553 uses 2-cyanopyrimidine as a raw material, under the conditions of methanol, water and hydrogen chloride, and palladium carbon catalytic hydrogenation method to prepare 2-aminomethylpyrimidine hydrochloride; US2004 / 142930 uses 2-cyanopyrimidine Pyrimidine is used as a raw material, and 2-aminomethylpyrimidine hydrochloride is prepared by nickel-catalyzed hydrogenation under ...

Examples

Embodiment 1

[0014] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to -10°C, add solid sodium methoxide in batches, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to -10°C, pass through A sufficient amount of hydrochloric acid gas was reacted for 2 hours, suction filtered and dried to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 89%.

Embodiment 2

[0016] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to -10°C, add sodium methoxide / methanol liquid dropwise, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to -10°C, pass Add sufficient amount of hydrochloric acid gas, react for 2 hours, suction filter, and dry to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 86%.

Embodiment 3

[0018] Add 2-aminomethylpyrimidine methanesulfonate into the reaction flask, cool down to 0°C, add solid sodium methoxide in batches, stir for 1 hour, filter with suction, put the filtrate back into the reaction flask, cool down to 0°C, and inject enough hydrochloric acid gas, reacted for 2 hours, suction filtered and dried to obtain 2-aminomethylpyrimidine hydrochloride with a purity greater than 99.5% and a yield of 88.5%.

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