14 results about "Compound E" patented technology

The invention discloses a preparation method of an SGLT2 inhibitor key intermediate, and belongs to the technical field of medicinal chemistry. The preparation method comprises the following steps: 1) reacting a compound B with trimethylchlorosilane under an alkaline condition to generate a compound C; 2) reacting the compound C with an aldehyde group reagent on an aromatic ring to generate a compound D; 3) reacting the compound E with a bromination reagent to generate a compound F; 4) preparing the compound F into a Grignard reagent to generate a compound G; 5) carrying out addition reaction on the compound D and a compound G to generate a compound H; and 6) carrying out dehydroxylation and trimethylsilyl protection on the compound H to generate a compound A. According to the preparation method, the risk caused by amplification of the Sandmeyer reaction in the original route is avoided, and meanwhile, the preparation cost of the key intermediate is greatly reduced.

The present application relates to the technical field of medicine, and in particular to a dihydrotricin, a preparation method and use thereof, the preparation method comprising the following steps: taking compound A, diisopropylethylamine and bromomethyl methyl ether to prepare compound B; taking compound C, diisopropylethylamine and bromomethyl methyl ether to prepare compound D; taking compound B and compound D, adding sodium hydroxide to prepare compound E; taking compound E, adding hydrochloric acid to prepare dihydrotricin after washing, separation, and concentration. The preparation method realizes efficient and large-scale synthesis of dihydrotricin. It is first confirmed that dihydrotricin can significantly resist A 1‑42 Oligomer-induced neurotoxicity has broad prospects in preventing and treating middle and late AD and delaying the progression of AD.

The invention belongs to the technical field of medicinal chemistry, and relates to a novel small nucleic acid drug intermediate and a preparation method thereof, the intermediate is a 2 '-FANA-dU phosphoramidite monomer, the preparation method comprises the following steps: 1, reacting a compound a with a 33% hydrogen bromide-acetic acid solution in dichloromethane, and performing post-treatment to obtain a compound b; 2, reacting uracil and the like to generate a white solid, and reacting the white solid with the compound b to obtain a compound c; 3, reacting the compound c in methanol and ammonia water, crystallizing and drying to obtain a compound d; 4, the compound d reacts with 4, 4 '-dimethoxytriphenylchloromethane, and a compound e is obtained through treatment; 5, the compound e reacts with anhydrous diisopropyl imidazole and a 2-cyanoethyl-N, N, N ', N'-tetraisopropyl phosphoramidite reagent, and the 2 '-FANA-dU phosphoramidite monomer is obtained.The 2'-FANA-dU phosphoramidite monomer prepared through the method can modify siRNA, the biological activity of the siRNA can be reserved or even enhanced, and the biological stability of the siRNA can be remarkably improved.

This invention discloses an isoflavone compound, its preparation method, and its applications. The compounds are derived by directional esterification modification of all phenolic hydroxyl groups with allyloxycarbonyl chloride, o-chlorobenzoyl chloride, or cinnamoyl chloride, using 4',7-dihydroxyisoflavone or 4',5,7-trihydroxyisoflavone as the parent nucleus. The invention also provides a mild and efficient preparation method for these compounds and confirms their significant anti-inflammatory pharmacological activity. Pharmacological studies show that compounds B and E, in particular, exhibit excellent in vitro and in vivo anti-inflammatory activity, with compound E showing superior activity compared to the positive control drug dexamethasone. These compounds can be used to prepare drugs for treating inflammatory diseases such as pneumonia and colitis.

The present invention discloses a method for preparing ketorolac tromethamine impurity E. The method for preparing compound E comprises the following steps: subjecting compound I to an amino acid condensation reaction in the absence of a solvent to produce compound E; the amino acid condensation reaction is carried out at a temperature of 120°C to 180°C. The method utilizes a solvent-free reaction, is simple to operate, and avoids the production of ester byproducts. High-purity compound E is obtained in good yield and meets the requirements for use as an impurity reference substance (purity greater than 95%).

This invention provides a process for preparing compound A, which is used to synthesize a KRAS inhibitor. [Solution] A process for preparing compound A as shown below is provided, comprising: (a) mixing a reactive compound containing 2-isopropyl-4-methylpyridine-3-amine or a salt thereof, a first base, and phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanate-2-isopropyl-4-methylpyridine (compound C); (b) mixing compound C and 2,6-dichloro-5-fluoronicotinamide to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridine-3-yl)carbamoyl)nicotinamide (compound E); and (c) mixing compound E and a second base to form a product mixture containing compound A and the second base. A process for synthesizing AMG 510 using compound A is also provided. JPEG2026071310000032.jpg35150

The invention is applicable to the technical field of biological medicine, and provides a self-assembled drug molecule and a preparation method and application thereof, and the preparation method comprises the following steps: synthesizing a compound Py-S-S-COOH; the method comprises the following steps: synthesizing a compound Py-S-S-B1RA; synthesizing a compound A; synthesizing a compound B; synthesizing a compound C; synthesizing a compound D; synthesizing a compound E; synthesizing a compound F; and the compound CBT-Gem-B1RA is synthesized through the synthesis of A chemotherapeutic drug gemcitabine and a targeted peptide bradykinin B1 receptor stimulant are coupled with a peptide fragment with self-assembly performance, so that the molecule has the capabilities of penetrating a blood brain barrier and targeting brain glioma, can smoothly enter a brain glioma part and can be self-assembled into nano particles in brain glioma cells, and the nano particles can be used for preparing a drug for treating brain glioma. The residence time of the drug in tumor cells is prolonged, the drug enrichment concentration is increased, and finally the glioma specific targeted therapy is realized.

The invention relates to zalpyrazolam, in particular to a preparation method of zalpyrazolam. The method comprises the following steps: carrying out nucleophilic substitution reaction on a compound A and a compound B to obtain a compound C; performing oxidation reaction on the compound C to obtain a compound D; performing reduction reaction on the compound D to obtain a compound E; carrying out nucleophilic substitution reaction on the compound E and a compound F to obtain a compound G, and carrying out ring closing reaction on the compound G and a compound H to obtain a compound I; the compound I is subjected to a thio reaction to obtain a compound J; performing ring closing reaction on the compound J and a compound K to obtain a compound L; performing demethylation reaction on the compound L to obtain a compound M; performing chlorination reaction on the compound M to obtain a compound N (zalpyrazolam); the invention provides a brand new preparation method of zalpyrazolam, which has the advantages of simple route, cheap and easily available raw materials, mild conditions and high reaction yield, and greatly reduces the production cost of zalpyrazolam.

The application relates to a preparation method of a compound F and a salt of the compound F, and a reaction as follows: comprising the following steps: (1) condensation reaction of compound B and compound C to prepare compound D; (2) reduction reaction of compound D to obtain compound E; (3) nitro reaction of compound E to prepare the compound F and the salt of the compound F. The application has the advantages of mild process conditions, simple operation, high yield, simple post-treatment, product obtained through only a purification mode of crystallization, reduction of "three wastes", and solution of the problems of the prior art, such as the need of ultralow temperature for reduction of methyl ester to aldehyde, difficulty in controlling selectivity, and easy over-reduction, ingenious integration of hydrogenation and salt formation reaction into a one-pot method, successful preparation of a hydrochloride crystal form of the compound F with high yield and high purity, stable crystal form, good reproducibility, and easy realization of industrialized production.

The invention discloses [1] rotaxane molecular compounds and a synthetic method thereof, and the synthetic method comprises the following steps: under the protection of inert atmosphere, carrying out nucleophilic substitution reaction on a compound A, sodium hydride and ethyl bromoacetate in N, N-dimethylformamide to obtain a compound B; performing nucleophilic substitution reaction with pyridine and trifluoromethanesulfonic anhydride to obtain a compound C; then carrying out a coupling substitution reaction with a compound D, bis (triphenylphosphine) palladium dichloride and 2-dicyclohexylphosphine-2 ', 4', 6 '-triisopropyl biphenyl to obtain a compound E; performing hydrolysis reaction with sodium hydroxide to obtain a compound F; under the protection of inert atmosphere, carrying out nucleophilic substitution reaction on the compound G, the compound H and potassium carbonate in N, N-dimethylformamide to obtain a compound I; performing hydrazinolysis reaction on the compound I and hydrazine hydrate to obtain a compound J; and under the protection of inert atmosphere, carrying out condensation reaction on the compound J, a compound F, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and 1-hydroxybenzotriazole to obtain the [1] rotaxane molecular compound.

The application discloses a preparation method of pemafibrate, which comprises the following steps: (1) reacting a compound SMA and a compound C to obtain an intermediate 1; (2) reacting the intermediate 1 with a compound D, and then performing sodium borohydride reduction to obtain an intermediate 2; (3) reacting the intermediate 2 with a compound E derivative to obtain an intermediate 3; and (4) performing hydrolysis reaction on the intermediate 3 to obtain the pemafibrate. According to the preparation method of the pemafibrate, the SMA and the compound C are used as starting materials, and the reaction temperature, the reaction time and the material ratio are strictly controlled, so that the yield and the purity of the product are high, the by-products are few, the post-treatment process is simple, column chromatography purification is not needed, and the preparation of subsequent high-quality products and impurity control are facilitated.

The application belongs to the field of organic synthesis and particularly relates to a preparation method of a Beclin1-ATG14L interaction inhibitor, a reaction formula of which is as follows: comprising the following steps: step (1): compound A is dissolved in an organic solvent, an acid catalyst is added to perform a ring closing reaction to obtain compound B; step (2): compound B is reacted with compound C in the presence of an organic solvent and a base to obtain compound D; and step (3): compound D is deprotected in the presence of an acid and an organic solvent to obtain compound E. The synthetic process route of the application is original, fills the blank of no preparation method of compound E at home and abroad, is simple in synthetic route, low in reaction equipment requirement, mild in reaction condition, easy to operate, high in yield, obtains multiple novel intermediates in the synthesis process, and the intermediates are stable in property, good in reusability and easy to realize industrialized scale production.

The invention discloses an oxytetracycline hydrochloride preparation and purification process, and relates to the technical field of medical chemistry. The preparation and purification process comprises the following steps: catalyzing a compound a serving as an initial raw material and a compound b through piperidine to obtain a compound c; reacting the compound c with a compound d to obtain a compound e; reacting the compound e with a compound f to obtain a compound g; performing photochemical isomerization on the compound g to obtain a compound h oxytetracycline hydrochloride crude product; and purifying the compound h oxytetracycline hydrochloride crude product by using a choline-lactic acid eutectic solvent to obtain oxytetracycline hydrochloride. According to the micro-channel reactor, precise control over the three-dimensional configuration is achieved in the micro-channel reactor through a 365 nm UV light source, 365 nm photon energy is precisely matched with trans-configuration pi-to-pi electron transition energy, trans-configuration pi electrons can freely rotate, and a cis-structure is formed. The problem of stereoisomerization in chemical synthesis is solved, and the isomerization yield is increased to 90% or above.