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Simple and convenient preparation method of key intermediate (2-methyl-4-amino-5-amino methyl pyrimidine) for vitamin B1

A technology of formamidomethylpyrimidine and aminomethylpyrimidine is applied in the field of production of vitamin B1 and derivatives thereof, can solve the problems of high reaction temperature, low yield, unfavorable environmental protection and the like, and achieves a simple and convenient operation with few steps. Effect

Active Publication Date: 2015-04-22
XINFA PHARMA
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Problems solved by technology

But the weak point of this route 3 is: use highly carcinogenic o-chloroaniline, the operation environment requirement is high, is unfavorable for environmental protection; o-Chloroaniline
The method has high reaction temperature, poor reaction selectivity, low yield, and is difficult to implement industrially

Method used

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  • Simple and convenient preparation method of key intermediate (2-methyl-4-amino-5-amino methyl pyrimidine) for vitamin B1
  • Simple and convenient preparation method of key intermediate (2-methyl-4-amino-5-amino methyl pyrimidine) for vitamin B1
  • Simple and convenient preparation method of key intermediate (2-methyl-4-amino-5-amino methyl pyrimidine) for vitamin B1

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preparation example Construction

[0037] A simple and convenient preparation method of vitamin B1 key intermediate 2-methyl-4-amino-5-aminomethylpyrimidine, comprising the following steps:

[0038] (1) Add 3-formylaminopropionitrile 2 to the reactor, add organic solvent to dissolve; add catalytic amount of Lewis acid; The molar ratio of acetamidine to 3-formylaminopropionitrile is (1-2): 1, and the molar ratio of acetamidine to 3-formylaminopropionitrile (1.1-1.3): 1 is preferred; Detection of 3-formamidopropionitrile reaction is complete; then continue,

[0039] (2) Add anisole internal standard and orthoformate triester 5, the molar ratio of the amount of orthoformate triester to the 3-formamidopropionitrile used in step (1) is (2-3):1, React at a temperature of 65-105°C, and use the gas phase to detect that the reaction is complete; 2-methyl-4-formylamino-5-formylaminomethylpyrimidine 6 is obtained; then continue,

[0040] (3) Directly add an aqueous solution of inorganic alkali, hydrolyze at 80-100°C to ...

Embodiment approach

[0054] According to the present invention, a preferred embodiment is as follows:

[0055] A kind of convenient preparation method of vitamin B1 key intermediate 2-methyl-4-amino-5-aminomethylpyrimidine, the steps are as follows:

[0056] a. Add 104.5 grams of acetamidine hydrochloride and 220 grams of 27wt% sodium methoxide methanol solution in a 1000 ml glass reaction vessel, react at 10-20°C for 30 minutes, filter, and the filtrate is a methanol solution of acetamidine;

[0057] b. Add 98 grams of 3-formylaminopropionitrile, 520 grams of toluene, and 27.2 grams of anhydrous zinc chloride into a 1000 milliliter four-necked flask; heat, and the internal temperature rises to 75-80 ° C; dropwise add the above-mentioned Acetamidine alcohol solution; stirring reaction, the use of gas phase detection 3-formamidopropionitrile reaction is complete. Then add 1 gram of anisole internal standard and 254.4 grams of trimethyl orthoformate; react at 95 to 100 ° C, and use gas phase detect...

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Abstract

The invention relates to a simple and convenient preparation method of a key intermediate (2-methyl-4-amino-5-amino methyl pyrimidine) for the vitamin B1. According to the method, lewis acid is used for catalyzing addition condensation reaction of acetamidine and 3-formyl amino ethyl cyanide and then catalyzing reaction of the condensation product and triethyl orthoformate to introduce a formyl chiral auxiliary, an imdo group and the formyl chiral auxiliary are subjected to ring formation to form 2- methyl-4-formyl amino-5- amino methyl pyrimidine, and finally basic hydrolysis is performed, so that 2-methyl-4-amino-5-amino methyl pyrimidine is obtained. The reaction procedures are carried out sequentially by adopting the one-pot method, the products in each step require no separation and purification, and the operation is simple and convenient. According to the method, highly toxic o-chloroaniline and other phenylamine compounds are not used, so that residue of o-chloroaniline compounds in the vitamin B1 product can be completely avoided. Meanwhile, the production wastewater is less and the yield is high.

Description

technical field [0001] The invention relates to a convenient preparation method of 2-methyl-4-amino-5-aminomethylpyrimidine, a key intermediate of vitamin B1, and belongs to the technical field of production of vitamin B1 and its derivatives. Background technique [0002] Vitamin B1, also known as thiamine or antineuritis, is a B vitamin composed of a pyrimidine ring and a thiazole ring. Vitamin B1 is stable in acidic solution, but unstable in alkaline solution, and is easy to be oxidized and decomposed by heat. [0003] The structural formula of vitamin B1 is as follows: [0004] [0005] Vitamin B1 is an important basic nutrient ingredient, and its synthesis and preparation have attracted much attention. Among them, 2-methyl-4-amino-5-aminomethylpyrimidine is a key intermediate commonly used in the preparation of vitamin B1. Regarding the synthesis of 2-methyl-4-amino-5-aminomethylpyrimidine, there are mainly three routes of cyanopyrimidine, formylpyrimidine and formy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/42
Inventor 朱成臣侯沧汤安于鞠立柱李新发
Owner XINFA PHARMA
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