Preparation method of chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate

Abstract

The invention provides a preparation method of chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate, and particularly relates to a preparation method of (3R,6R) -1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate. The preparation method comprises the steps of taking Boc-D-alanine and L-serine methyl ester hydrochloride as initial raw materials, and preparing the chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate through condensation reaction, deamination protection, ring closing reaction, reduction reaction, amino protection, oxidation reaction, ring closing reactionand ring opening reaction. According to the preparation method provided by the invention, the Boc amino protective agent is used for protecting amino, so that the production cost is reduced, the rawmaterials are easy to obtain, the conditions are mild, the yield is relatively high, and the preparation method can be applied to large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a preparation method of chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1,3-dicarboxylate. Background technique [0002] Piperazine compounds are important nitrogen-containing heterocycles in heterocyclic compounds. Piperazine derivatives have been valued for their anti-depressant, anti-inflammatory, analgesic, and anti-tumor activities. In addition, the 1,4-position of the piperazine ring is a basic group. The group has good water solubility and alkalinity, so introducing it into the drug molecule can increase the water solubility of the drug, effectively regulate the acid-base balance of the drug, and thereby enhance the biological activity of the drug molecule in animals and plants. [0003] CN110183471A discloses a novel piperazine derivative and its preparation method and application. The compound is (R)-6-methyl-3-(4-(isopropylsulfonyl)phenyl)...

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Problems solved by technology

[0003] CN110183471A discloses a novel piperazine derivative and its preparation method and application. The compound is (R)-6-methyl-3-(4-(isopropylsulfonyl)phenyl)-6-chloro-1H -pyrrolo[2,3-b]pyridine)-4,5,6,7-tetrahydropyrazolo[1,5-a]piperazine, the technique is based on 1((R)-2-(benzyl Amino)propan-1-ol) and 2(3-formyl-4-bromopyrazole) as starting materials, the new piperazine derivatives prepared can effectively inhibit the proliferation of human breast cancer cells, and with Adriamycin The combined use of these factors has a good synergistic anti-human breast cancer cell effect, and the preparation process conditions of the compound are relatively mild, which overcomes the disadvantages of harsh synthesis conditions, low yield, and unsuitability for industrial production of piperazine compounds

[0009] The above preparation method needs to go through 8 reaction processes, and includes two processes of removing Cbz-protected amino groups. In the process of removing Cbz-protected amino groups, palladium carbon is used as a catalyst. Palladium carbon is expensive, which increases production costs and is not conducive to industrial production.

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