23 results about "Compound E" patented technology

Provided herein is a pharmaceutical combination and a use thereof, particularly relates to a pharmaceutical composition comprising: (a) Compound A or Compound C, or a pharmaceutically acceptable salt thereof, or a co-crystal thereof; in combination with (b) Compound B, Compound D or Compound E, or a pharmaceutically acceptable salt thereof, or a crystal thereof.

The invention relates to the technical field of drug synthesis, and discloses a preparation method of a lysine-specific demethylase 1 (LSD1) inhibitor key intermediate, and the preparation method of the intermediate comprises the following steps: step 1, esterification reaction: reacting a compound A with a symmetric carbonylation reagent X to generate an asymmetric carbonate compound B; step 2, amine-ester exchange reaction: exchanging ester groups in the compound B with amine groups in the compound C to generate an amide compound D; step 3, cyclization reaction: converting carbonyl in the compound D into epoxy substituent in the compound E; and 4, fluorination reaction: reacting the compound E with a fluorination reagent, and carrying out ring opening to generate a fluorine substituted compound F. The preparation method comprises the following steps: oxidizing a key intermediate of the LSD1 inhibitor, connecting the key intermediate with an amine fragment, and performing functional group modification to obtain the fluorine-substituted cyclopropylamine compound with LSD1 inhibitory activity, thereby achieving the beneficial effect that the fluorine-substituted cyclopropylamine compound with LSD1 inhibitory activity can be conveniently and quickly synthesized from the intermediate.

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 invention belongs to the technical field of medicinal chemistry, and particularly relates to a nicardipine hydrochloride intermediate as well as a preparation method and application thereof. The nicardipine hydrochloride intermediate compound E provided by the invention is oxalate, is in a solid form, is stable in property and can be used for preparing nicardipine hydrochloride. The invention also relates to a preparation method of the compound E and application of the compound E, namely the compound E can be used for preparing nicardipine hydrochloride. The intermediate compound E is prepared by adopting a one-pot method, the post-treatment process is greatly simplified, the operation is simple, the cost is low, the purity is good, the yield is high, and the method is more suitable for industrial production. The method for preparing nicardipine hydrochloride by using the intermediate E is low in cost, the total yield is greater than 60%, the purity is greater than or equal to 99.9%, and the method is more suitable for industrial production.

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%).

The invention relates to a preparation method of a compound G. The preparation method comprises the following steps: step 3, mixing a compound D and an organic solvent, adding alkali and a condensing agent for activating reaction, and then adding a compound E for condensation reaction to obtain a compound F; 4, removing a protecting group from the compound F to obtain a compound G; r < 2 > is selected from Boc, Tos and Trt, and R < 2 > is selected from a group consisting of Boc, Tos and Trt; and n is 0-8. The invention provides a novel compound C'and a preparation method thereof, the novel compound C 'is used for preparing a compound F, a compound G and a compound I at high yield, the reaction operation of each step is simple, the reaction is stable and controllable, the raw material loss is reduced, the post-treatment is simple, the purification cost in the production process can be reduced, the industrial amplification production is facilitated, and the novel compound C' has higher commercial value.

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 belongs to the field of organic synthesis, and particularly relates to a preparation method of a Beclin1-ATG14L interaction inhibitor, the reaction formula is as follows: # imgabs0 #, and the preparation method comprises the following steps: step (1), dissolving a compound A in an organic solvent, adding acid for catalysis, and carrying out ring closing reaction to obtain a compound B; (2) reacting the compound B with a compound C in the presence of an organic solvent and alkali to obtain a compound D; and step (3): performing deprotection on the compound D in the presence of acid and an organic solvent to obtain a compound E. The synthesis process route is original, the blank that no compound E preparation method exists at home and abroad is filled, the synthesis route is simple, the requirement for reaction equipment is low, the reaction condition is mild, operation is easy and convenient, the yield is high, multiple brand-new intermediates are obtained in the synthesis process, the intermediates are stable in property and good in reproducibility, and industrial large-scale production is easy to achieve.

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 invention provides a preparation method of an inositol hexaphosphate kinase inhibitor, and provides a preparation method of a compound shown as a formula F. The reaction formula is shown as the following: # imgabs0 #, in which R1 is OMs, OTf, OTs, Cl, Br or I; comprising the following steps: (1) carrying out carbonyl insertion reaction on a compound A, ethanol and a CO source in the presence of a palladium catalyst and alkali to generate a compound B; (2) performing deprotection reaction on the compound B in a hydrochloric acid solution to generate a compound C; (3) in the presence of a reducing agent and an acid activator, carrying out reductive amination reaction on the compound C and a compound D to generate a compound E; (4) carrying out hydrolysis reaction on the compound E under an alkali condition to generate a compound F; the preparation method disclosed by the invention is simple and convenient to operate, high in yield, good in product quality, mild in reaction condition, easily available in raw materials, short in reaction time and suitable for industrial large-scale production.

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 invention relates to a preparation method of a pyrazole bipyridazine compound, which comprises the following steps: (1) reacting a compound A with a compound B to obtain a compound C; wherein R1 is selected from a C1-C12 straight chain or branched chain alkyl group or a C3-C8 cycloalkyl group, and R2 is selected from hydrogen or a C1-C12 straight chain or branched chain alkyl group; (2) when R2 is C1-C12 linear chain or branched chain alkyl, the compound C is subjected to a hydrolysis reaction to obtain a compound C-1; reacting the compound C-1 with hydrazine to obtain a compound D; when R2 is hydrogen, the compound C reacts with hydrazine to obtain a compound D; and (3) reacting the compound D with a chlorination reagent to obtain a compound E. The preparation method provided by the invention mainly adopts a conventional reaction, avoids a Grignard ultralow-temperature reaction or a noble metal catalytic reaction, and is mild in reaction condition, low in comprehensive cost, easy in reaction implementation and beneficial to industrial production.

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.

The invention discloses a quaternary cycloalkanated quaternary carbon beta amino acid derivative compound E, an intermediate compound and a preparation method of the quaternary cycloalkanated quaternary carbon beta amino acid derivative compound E. The structural general formula of the quaternary carbon beta amino acid derivative is # imgabs0 #, R1 is alkyl, R2 is amino protecting group, and R3 is hydrogen atom, fluorine atom, chlorine atom, trifluoromethyl, methoxyl and methyl. The chiral beta amino acid derivative can be obtained by adopting a cobalt chloride catalytic reduction method, so that the reaction time is shortened, the production cost is reduced, the reaction yield is improved, and the blank of a beta amino acid derivative synthesis method is filled.

The invention provides a key intermediate compound G of relagoride and a preparation method thereof, and belongs to the technical field of medicine synthesis. The intermediate is a compound as shown in a chemical formula (G), and the preparation method comprises the following steps: (1) under the condition that an initiator azodiisobutyronitrile participates in, a compound D reacts with N-bromosuccinimide to obtain a compound E; (2) reacting the compound E with dimethylamine hydrochloride to obtain a compound F; and (3) carrying out hydrolysis reaction on the compound F under the action of alkali to obtain the relugolix intermediate compound G. The method is mild in reaction condition, high in reaction yield, easy in product purification, low in production cost, green, environment-friendly and suitable for commercial scale.