37 results about "Dieckmann condensation" patented technology

The invention belongs to the field of drug synthesis and relates to an entecavir compound and a synthetic method of an intermediate of the entecavir compound. The novel synthetic method comprises: by taking (S)-3-hydroxyl dimethyl adipate as an initial raw material, preparing an intermediate 9 through hydroxyl TBS protection, Dieckmann condensation reaction, ketone protection to ketal, ester group reduction to hydroxyl, hydroxyl protection, deprotection, ketone to silyl enol ether and Rubottom oxidizing reaction; and preparing entecavir from the intermediate 9 through wittig reaction, Mitsunobu reaction, silicon preventing radical group removal and basic hydrolysis. The novel synthetic method provided by the invention is mild and easily controllable in reaction condition, simple to operate, high in product yield, high in purity and suitable for industrialized mass production.

The invention provides 2, 3, 5, 7-tetrasubstituted dihydro-pyrazolo piperidine derivative and a preparation method and application thereof. The derivative is 2, 3-bis(substituted phenyl)-5-subsituted arylmethyl-7-substituted benzylidene dihydro-pyrazolo piperidine derivative, having the following formula (I). The preparation method includes using substituted arylmethyl amine and methyl acrylate as raw materials; subjecting the materials to Michael addition, Dieckmann condensation and hydrolysis-decarboxylation sequentially; allowing for Aldol reaction with substituted benzaldehyde to obtain intermediate N-substituted arylmethyl-3, 5-bis(substituted benzylidene)-4-piperidone; allowing for condensation with substituted phenylhydrazine to obtain a compound according to the formula (I). The derivative is efficient in inhibiting multiplication of various carcinoma cell lines such as leukemia, esophagus cancer, ovarian cancer and breast cancer in human, is well stably metabolic in liver microsomes of human and rat, is free of direct and competitive inhibition on five enzymes of liver microsomes, such as CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19, is highly bioavailable, is low in toxicity to normal cells, and is available for the preparation of drugs for the cancers.

The invention provides a tetrahydropyridopyridone derivative as shown in a general formula (I), and a preparation method thereof. The method comprises the following steps of: preparing N,N-bi(methoxycarbonyl group) substituted benzylamine (b) by carrying out Michael addition on substituted benzylamine (a) and methyl acrylate, carrying out Dieckmann condensation on (b) under the action of sodium alcoholate, subsequently carrying out hydrolysis and decarboxylation under the action of acid so as to obtain N-substituted benzyl-4-piperidone (d), carrying out an aldol condensation reaction on (d) and bimolecular aromatic aldehyde so as to obtain N-substituted-3,5-bi(substituted benzylidene piperidine-4-ketone (e), and refluxing and heating (e) malononitrile and ammonium acetate in ethanol so as to obtain a final product as shown in the general formula (I). The tetrahydropyridopyridone derivative is simple in process and convenient to produce in scale, and the compound (I) has a good inhibition effect on multiplication of leukemia K562 cells, ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells. Therefore, the invention further provides an application of the compound as shown in the general formula (I) in preparing medicaments for preventing multiplication of the leukemia K562 cells, the ovarian cancer HO-8910 cells and the liver cancer SMMC-7721 cells.

The invention relates to a Dolasetron isomer or salt thereof, a preparation method for the Dolasetron isomer or salt thereof and application of the Dolasetron isomer or salt thereof. In the preparation method, the Dolasetron isomer or salt thereof is prepared from outside-hexahydro-8-hydroxy-2,6-methylene-2H-quinolizidine-3(4H)-ketone or salt thereof serving as a raw material by esterifying and salifying. The invention also provides two methods for synthesizing outside-hexahydro-8-hydroxy-2,6-methylene-2H-quinolizidine-3(4H)-ketone. The outside-hexahydro-8-hydroxy-2,6-methylene-2H-quinolizidine-3(4H)-ketone is prepared from the compound (6) shown in the specification and serving as a raw material by the steps of reducing, protecting hydroxyl, performing Dieckmann condensation and performing hydrolysis and decarboxylation, or by the steps of reducing, performing Mitsunbu esterification, performing hydrolysis, protecting hydroxyl, performing Dieckmann condensation and performing hydrolysis and decarboxylation. The invention also relates to application of the Dolasetron isomer or the salt thereof to preparation of Dolasetron, or application of the salt of the Dolasetron isomer to preparation of control products for detection.

The invention discloses a N-substituted benzyl tetrahydropyridine with -5-substituted indole and preparation method and application thereof, and the structure is shown in the general formula (I): substituted benzene methylamine (ethylamine) and methyl acrylate are raw materials, and an intermediate N-substituted benzylpiperidine (phenylethylpiperidine)-4-ketone is obtained by three steps of reaction such as Michael addition, Dieckmann condensation and hydrolysis decarboxylation or the like in sequence, and the object (I) is obtained by condensation reaction of the intermediate and 5-substituted indole. The compound (I) can effectively inhibit proliferation of human leukemia K562, Jurkat, U937, THP-1 cell line, the human esophagus cancer ECA-109 cell line, human liver cancer SMMC-7721 cell line, human ovary cancer HO-8910 cell line, human breast cancer MCF-7 cell line, breast cancer MDA-MB-231 cell line; the compound has a good metabolism stability in the human and rat liver microsomes; The compound does not have mechanical inhibition effects for five enzymes of human liver microsomes such as CYP3A4, CYP 2D6, CYP2C9, CYP1A2 and CYP2C19 or the like; the compound can induce the cell cycle G2 / M retardance and promote cancer cell apoptosis and inhibit cancer cell propagation.