A kind of method of synthesizing chlorambucil

Abstract

The invention discloses a method for synthesizing chlorambucil, which relates to the technical field of organic chemistry, and comprises the following steps: S1, the proportion content is 10.83%: 10.83% - 32.50%: 0.22% - 2.17%: 0.43% - 2.17%: 10.83%-54.17%: 10.83%-54.17% of 4-bromo-N,N-bis(2-chloroethyl)aniline, N-(quinolin-8-yl)but-3-enamide, Add the mixture made of palladium chloride, tri-n-butylphosphine tetrafluoroborate, potassium carbonate, benzoic acid and dimethyl sulfoxide in a molar volume ratio of 0.1mmol: 2mL to the reaction vessel and mix well; S2. The reaction vessel was placed in an oil bath at 135-145° C. and stirred vigorously for 24 hours. The present invention controls the region and chemoselectivity in the reaction by designing 8-aminoquinoline as a compound with a leaving group through a coupling reaction, effectively solving the problem of too many steps in the synthesis process of the existing chlorambucil problem, and the present invention has the characteristics of high reaction regioselectivity and yield, mild reaction conditions, and simple reaction and post-treatment purification process.

Description

technical field [0001] The invention relates to the technical field of organic chemistry, in particular to a method for synthesizing chlorambucil. Background technique [0002] Chlorambucil (CB-1348, leukeran) belongs to aromatic nitrogen mustard, white crystal, m.p.64~67℃, insoluble in water, soluble in ethanol and chloroform, etc. Chlorambucil was synthesized in the 1950s , the four-carbon lipid chain in the molecule increases the lipophilicity of the molecule, while the free carboxylic acid increases the hydrophilicity, and the partition coefficient in benzene / water is 0.67. The mechanism of action of chlorambucil is the same as that of other chlorambucil drugs, mainly caused by The cross-linking of DNA chains affects the function of DNA. The drug resistance is mainly due to the increased activity of glutathione S-transferase. After this product enters the human body, the propionic acid side chain is oxidized to chlorambucil at the β-position. The anti-tumor effect of mu...

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Problems solved by technology

[0002] Chlorambucil (CB-1348, leukeran) belongs to aromatic nitrogen mustard, it is white crystal, m.p.64~67℃, insoluble in water, soluble in ethanol and chloroform, etc. Chlorambucil was synthesized in the 1950s , the four-carbon lipid chain in the molecule improves the lipophilicity of the molecule, while the free carboxylic acid increases the hydrophilicity, and the partition coefficient in benzene / water is 0.67. The mechanism of action of chlorambucil is the same as that of other nitrogen mustard drugs, mainly causing The cross-linking of DNA chains affects the function of DNA. Drug resistance is mainly due to the increase in the activity of glutathione S-transferase. The anti-tumor effect of mustard is lower than that of chlorambucil, but the dechlorination ethyl effect is slow, so the action time is longer, and it is mainly used for chronic lymphocytic leukemia, ovarian cancer and low-grade non-Hodgkin's lymphoma

[0003] The existing synthetic method of chlorambucil generally has many synthetic steps, poor reaction regioselectivity, low product yield, mild reaction conditions, complex reaction and post-treatment purification process, etc.

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