1196713-21-9Relevant articles and documents
Preparation method of intermediate for synthesizing antitumor medicine niraparib and intermediate
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, (2019/02/17)
The invention discloses a preparation method of an intermediate for synthesizing an antitumor medicine niraparib and the intermediate. The invention discloses a preparation method of a compound f, which comprises the following step: in a solvent, under the effect of alkali, performing ring-closure reaction as a formula shown below on a compound e to obtain the compound f. The preparation method does not relate to the steps of noble metal catalytic reduction or noble metal catalytic coupling and chiral resolution; the requirement on the equipment is low; the operation is simple; the industrialproduction is facilitated; the generation of heavy metal-containing and phosphorous waste liquid can be avoided; the cost is low; the product ee value is high. The formula is shown in the description.
Synthesis method for (R)-3-phenylpiperidine or/and (S)-3-phenylpiperidine and synthesis method for chiral intermediate of niraparib
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, (2018/07/10)
The invention belongs to the technical field of organic synthesis. The synthesis method firstly provided by the invention takes benzyl-4-oxopiperidine as a starting material, and the starting materialis subjected to Grignard reaction, elimination reaction, hydrogenation reduction reaction and chiral resolution in sequence to successfully obtain a target product (R)-3-phenylpiperidine or/ and (S)-3-phenylpiperidine. The synthesis method sencondly provided by the invention takes the same starting raw material for Grignard reaction, organic silicon reagent is used for removing a hydroxide radical, and benzyl is removed by catalytic hydrogenation reaction; finally, the chiral resolution is carried out to obtain a target product. The (S)-3-phenylpiperidine can be synthesized according to the synthesis method. (S)-3-p-aminosalicylic phenylpiperidine can be synthesized according to the third aspect; or according to the fourth aspect, (S)-3-p-bromophenyl piperidine is synthesized to serve asthe key intermediate for preparing the niraparib. According to the synthesis method for (R)-3-phenylpiperidine or/ and (S)-3-phenylpiperidine and the synthesis method for chiral intermediate of niraparib, production cost is obviously lowered, and the synthesis methods are favorable for the large-scale industrial production of a niraparib medicine.
Preparation method of Niraparib intermediate 4-(3S-piperidine-3-yl)aniline
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, (2017/04/03)
The invention discloses a preparation method of a Niraparib intermediate 4-(3S-piperidine-3-yl)aniline. The preparation method is characterized by comprising the following steps: 1) carrying out a contact reaction on a compound shown as a formula I and hydroxylamine hydrochloride to obtain a compound shown as a formula II; 2) carrying out a catalytic reaction on the compound shown as the formula II in the presence of phenyl dichlorophosphate to obtain a compound shown as a formula III; 3) carrying out a reduction reaction on the compound shown as the formula III to obtain the Niraparib intermediate 4-(3S-piperidine-3-yl)aniline shown as a formula X. A specific reaction process is shown in the description. By adopting the method provided by the invention, the utilization of a metal catalyst and transaminase with a high price is avoided, so that the production cost is lower, and a target product has high yield and stereoselectivity.