121 results about "Pyrimidifen" patented technology

The invention relates to pyrimidinamine and pyridinamine Hedgehog signal conduction inhibitors. The inhibitors are compounds with the structure represented by formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to a medicinal use of the above compounds as hedgehog signal conduction inhibitors.

The invention discloses preparation methods and biological activity of amino acid ester type compounds containing 4-(dimethoxymethyl)pyrimidine heterocycle for prevention and treatment of tobacco mosaic viruses, namely compounds as shown in the following general formula (I) and preparation methods thereof. The invention introduces amino acid ester type compounds containing 4-(dimethoxymethyl)pyrimidine heterocycle synthesized by a one-pot process under an ultrasonic condition by taking 4-(dimethoxymethyl)pyrimidine-2-amine, substituted aldehyde and malonic ester as raw materials and takes toluene as a solvent. The compounds I5 and I8 disclosed by the invention have better inhibition effects on tobacco mosaic viruses and ralstonia solanacearum. The compounds are shown in the description.

The invention relates to an acaricide composition prepared by using pyrimidifen and etoxazole as main ingredients and adding emulsifier as well as organic solvent. The composition has the advantages of special effects on preventing and eliminating mite and ovum thereof, larva and nymphae, simple processing technique, no three wastes and convenient use.

The present invention relates to a compound containing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-( trifluomethyl) pyrrol-3-formonitrile and one or several kinds selected from pyrazole, imidazole, triazole, pyrimidine amine and thiocarbamate, etc. Said invention can effectively be used for preventing and controlling the injurious insects, mites and diseases of cotton, fruit tree, tea, vegetable,flower and crops, etc.

The present invention relates to new organic compound, and is especially the preparation process of N-(2-methyl-5-nitro) phenyl-4-(3-pyridyl) pyrimidiyl-2-amine as the key intermediate for imatinib, which is tyrosine protein kinase inhibitor for treating chronic myeloid leukemia and other diseases, and its analog N- phenyl-pyrimidiyl-2-amine derivative. The target product may be prepared through condensation of 4-aromatic heterocycle-2-halogenated pyrimidine and substituted aniline in the presence of catalyst. The preparation process has low material cost, scientific synthesis path, high product yield and other advantages.

The invention discloses an N-[(3R,4R)-1-benzyl-4-methylpiperidine-3-yl]-N-methyl-7H-pyrrolo[2,3-d] pyrimidine-4-amine crystal and a preparation method thereof. The method comprises steps as follows: firstly, 4-chloro-7-(p-tolylsulfonyl) pyrrolo [2,3-d] pyrimidine, 1-benzyl-4-methyl-3-aminomethyl dihydrochloride, potassium carbonate and water are added to a reaction vessel sequentially, heated and subjected to thermal insulation, and white solids are obtained; the white solids, sodium hydroxide and n-butyl alcohol are added to the reaction vessel sequentially, an obtained organic phase is washed with water, then anhydrous magnesium sulfate is added to the organic phase for dehydration, and a dichloromethane extracting solution is obtained; finally, eluting and curing are performed, and the crystal is obtained. The purity of the crystal is higher than 99.9%. According to a final product tofacitinib citrate synthesized with the intermediate, related substances are controlled to be lower than 0.1%, and the preparation of the crystal has great technical advantage and research value.

The present invention relates to crystalline forms of 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine salts; processes for the production thereof; pharmaceutical compositions thereof; and methods for inhibiting tumor growth therewith.

The invention provides a deuterated benzimidazole-pyrilamine derivative which is a compound shown in formula (I) shown in the specification or a pharmaceutically acceptable salt, a monocrystal substance or a polymorphic substance of the compound as well as an application of the derivative to preparation of drugs for treating cancer, and further provides pharmaceutical composition containing the compound. R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 and R16 refer to hydrogen or deuterium independently, and at least one deuterium is contained in total. The deuterated benzimidazole-pyrilamine derivative mesylate prolongs half-life periods of the drugs, prolongs the retention time of the drugs in human bodies and increases concentration of the drugs in blood, so that the better curative effect can be realized.

A synergistic composite insecticide for preventing and treating rice borer, beet noctuid and high-resistance plutella xylostella larva contains two primary active components including high-effect cypermethrin, assistant and excipient.

The invention provides a preparation method of a compound 2-[2-(dimethylaminoethyl) methylamino]-3-acrylamido-5-[4-(1-methyl-1H-indole-3-yl) pyrimidine-2-amino]-6-(2, 2, 2-trifluoroethoxy) pyridine asshown in a formula I, a used intermediate and a preparation method of a related intermediate. According to the method, 3-(2-chloropyrimidine-4-yl)-1-methyl-1H-indole and a compound shown as a formulaVII are subjected to a condensation reaction, a substitution reaction, a reduction reaction, an acylation reaction and an elimination reaction, and a compound shown as a formula I is obtained. The preparation method disclosed by the invention is environment-friendly, low in cost, mild in condition, simple to operate, high in yield, high in final product purity and suitable for industrial production.

The present invention relates to a novel N-phenyl-2-pyrimidine-amine derivative represented by the above formula (1) and its salt showing a superior effect on cancer in warm-blooded animals, such as lung cancer, gastric cancer, colon cancer, pancreatic cancer, hepatoma, prostatic cancer, breast cancer, chronic or acute leukemia, hematologic malignancy, encephalophyma, bladder cancer, rectal cancer, cervical cancer, lymphoma, etc. The present invention also relates to a process for preparing the compound, and to a pharmaceutical composition for the treatment of the above various diseases, which comprises an effective amount of the compound as an active ingredient together with pharmaceutically acceptable inert carriers.

A synergistic composite insecticide for preventing and treating cabbage caterpillar and rice borer contains two primary active components including high-effect cyfluthrin, assistant and excipient.

The invention relates to a synthesis method of imatinib and imatinib mesylate. The method comprises the following steps: condensing 3-acetylpyridine and N,N-dimethylformamide dimethyl acetal which aretaken as initial raw materials to obtain 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one, then reacting with 2-methyl-5-nitrophenylguanidine nitrate to form a pyrimidine ring, performing nitro reductionto obtain N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine, amidating the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine and 4-(chloromethyl)benzoyl chloride, performing affinitysubstitution with 1-methylpiperazine to obtain imatinib, and salifying the imatinib and methanesulfonic acid. The products obtained by the method have the advantages of few impurities, simplicity in post-treatment, high total yield, greenness, environmental protection and safety, and is suitable for a production process for large-scale industrial production of imatinib mesylate.

The invention discloses a Tofacitinib midbody, i.e. a new crystalline form of N-methyl-N-((3R,4R)-4-methyl-1-benzyl-3-piperidyl)-7H-pyrrolo[2,3-D]pyrimidine-4-amine, a preparation method thereof, and a method of preparing Tofacitinib by using a midbody of the crystal form. The midbody of the crystal form has the advantages of high purity, good stability, simple preparation, easy production and sales.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tofacitinib citrate intermediate as well as a preparation method and an application thereof. Whereinthe tofacitinib citrate intermediate is N-methyl-N-((3R, 4R)-4-methylpiperidine-3-yl)-7H-pyrrolo [2, 3-D] pyrimidine-4-amine dihydrochloride monohydrate. The preparation method comprises the followingsteps: adding N-methyl-N-((3R, 4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo [2, 3-d] pyrimidine-4-amine into water and an organic solvent, then adding hydrochloric acid and palladium hydroxide carbon, introducing hydrogen to react, and filtering out the palladium hydroxide carbon; cooling to room temperature, dropwise adding an organic solvent, crystallizing, carrying out suction filtration, and drying to obtain the tofacitinib citrate intermediate. The method greatly improves the utilization rate of raw materials, reduces the production cost, and improves the product quality.

Preparation methods of N-(2-methylpyridyl-5-nitro-3)-4-(3-pyridinyl)pyrimidin-2-amine and an intermediate thereof are characterized in that N-(2-methylpyridyl-5-nitro-3-)-4-(3-pyridinyl)pyrimidin-2-amine is prepared through three step reactions by taking 2-sulfydryl-4-(3-pyridinyl)pyrimidine as a raw material; wherein 2-sulfydryl-4-(3-pyridinyl)pyrimidine is subjected to combination of two reactions comprising iodomethane methylation and oxidation by one-pot synthesis to direct synthesize 2-methylsulfonyl-4-(3-pyridinyl)pyrimidine; then the prepared compound 2-methylsulfonyl-4-(3-pyridinyl)pyrimidine by using the above method is reacted with a raw material compound 2-amino-4-nitrotoluene to obtain the product N-(2-methylpyridyl-5-nitro-3-)-4-(3-pyridinyl)pyrimidin-2-amine. The preparation methods have the advantages that no organic solvent is needed to add during the whole process, product processing is simple, yield is high and pollutant discharge is less.

The present disclosure provides a method of regioselective synthesis of an imidazo-pyrimidine compound of formula (XXa) or (XXb), the method comprising the step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2. The cyclization reaction of imidazo [1, 2-a] pyrimidine-amine generated between beta-ethoxy acrylamide and phosphorylated aminoimidazole depends on the guiding effect from the phosphorylated aminoimidazole in the ring and the phosphorylated aminoimidazole outside the ring. According to the reaction, the 2-amino or 4-amino structure isomer of the imidazo [1, 2-a] pyrimidine is generated in a good yield and a regioselectivity range of 90: 10 to 99: 1. The reactions can be used to synthesize a variety of tracer molecules for neurological condition research, such as where R3 and R4 together with the imidazole ring atom to which they are bonded form a benzene ring, and the product is a substituted benzimidazopyrimidine. The reaction may be summarized to form imidazo [1, 2-a] pyrimidines substituted at its 2-and 4-positions with alkoxy or thioalkyl groups.

Disclosed herein are tricyclic compounds, including pyrimido[4',5':4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3',2M,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2',3':4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3',2':4,5]furo[3,2-d]pyrimidin-4- amine, and pyrimido[4',5':4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholinereceptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disordersassociated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

The invention discloses compounds represented by the formula (I), stereoisomers, pharmaceutically acceptable salts, or solvates thereof. The invention also provides an application of the abovementioned compounds in the preparation of antitumor drugs, angiogenesis inhibitors, EFGR kinase inhibitors, or AUR A kinase inhibitors.

The invention discloses a preparation method of imatinib mesylate. The method comprises the following steps: chlorinating imatinib acid[4-(4-methylpiperazine-1-ylmethyl)benzoic acid dihydrochloride] with thionyl chloride to generate an imatinib mesylate intermediate I; condensing the imatinib mesylate intermediate I with imatinib amine [N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine] toobtain an imatinib mesylate intermediate II, and finally salifying the imatinib mesylate intermediate II with methanesulfonic acid to obtain imatinib mesylate. According to the invention, the raw materials imatinib acid and imatinib amine used in the method are common medical intermediates, other raw materials and reagents used in the process are convenient and easy to obtain, the reaction process and post-treatment operation are simple and convenient, the yield is high, and the production cost is effectively reduced through process optimization.

The invention provides a preparation method of a tofacitinib impurity, and relates to the field of drug synthesis and drug quality research. The preparation method comprises the steps of dissolving N-methyl-N-((3R, 4R)-4-methylpiperidine-3-yl)-7H-pyrrolo [2, 3-d] pyrimidine-4-amine dihydrochloride in a first organic solvent, and reacting with methyl 3-chloro-3-oxopropionate under the catalysis of an acid-binding agent to obtain 3-((3R, 4R)-4-methyl-3-(methyl (7H-pyrrolo [2, 3-d] pyrimidine-4-yl) amino) piperidine-1-yl)-3-oxopropionic acid methyl ester,dissolving the product in a second organic solvent, adding an alkaline reagent, and adjusting the pH value to be acidic, thereby obtaining the tofacitinib impurity. The tofacitinib impurity is 3-((3R, 4R)-4-methyl-3-(methyl (7H-pyrrolo [2, 3-d] pyrimidine-4-yl) amino) piperidine-1-yl)-3-oxopropionic acid. The method is simple, and the product is high in yield and purity.

The invention relates to a preparation method of imatine, and belongs to the technical field of medicine synthesis. In order to solve the problem of low product yield in the prior art, the invention provides the preparation method of the imatrine, which comprises the following steps: under the action of a catalytic amount of nitroreductase and coenzyme, converting a compound N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidinamine shown as a formula II into the imatrine through an enzymatic reaction; wherein the nitroreductase is as shown in SEQ NO1. According to the method, nitryl can be effectively and efficiently converted into amino, other by-products cannot be generated due to side reaction of the raw materials in the reaction process, the method has the advantages of being low in impurity content and high in product conversion rate, and the product yield reaches 97% or above.

The invention relates to a substituted benzo or pyridopyrimidine amine inhibitor as well as a preparation method and application thereof. Specifically, the compound has a structure as shown in a formula (I), the invention further discloses a preparation method of the compound and application of the compound as an SOS1 inhibitor, and the compound has a very good selective inhibition effect on SOS1 and has better pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.

The present invention discloses a compound used as a general formula (I) of protein kinase inhibitor, the salt accepted pharmaceutically and the preparation method; wherein, X is -(CH2)m-COO-; m is equal to 1 to 5 or direct bond; Y is -(CH2)n-O- or -(CH2)n-PhO-; n is equal to1 to 10 or direct bond; the preparation method comprises a step which uses N-(5-amino-2- methyl-phenyl)-4- (3-pyridyl)-2-pyrimidinamine and general formula (II) compound as raw material synthesis. The present invention also discloses the preparation method of the compound, comprising the compound and the treatment of being used as tyrosine protein kinase inhibitor in diseases such as cancer relative to tyrosine in particular to Bcr-Abl.

The invention relates to a mite-killing composition containing pyrimidifen and pyridaben. An active ingredient is formed by compounding pyrimidifen and pyridaben in a binary manner, wherein the mass ratio of the pyrimidifen to the pyridaben is (1-40):(40-1). The total mass of the active ingredients of the pyrimidifen and the pyridaben in a preparation accounts for 1%-80% of the mass of the whole preparation, and the balance is an auxiliary ingredient which is allowable and acceptable in pesticides. The mite-killing composition can be prepared into forms such as missible oil, suspending agent, wettable powder, water dispersible granules, emulsion in water and microemulsion. The mite-killing composition can be used for preventing tetranychid mites and rust mites on oranges, apples, pears, hawthorns, cottons, tobaccos, tea leaves, vegetables, ornamental plants and the like.

The invention provides a (substituted phenyl) (substituted pyrimidine) amido derivative as shown in a general formula (I) defined in the description, an optical isomer thereof, a pharmaceutically acceptable salt or eutectic, a preparation method thereof, and application thereof in preparation of tumor drugs. The general formula is a compound (I).

The invention relates to an application of composition containing a heterocyclic compound in preparation of a drug for treating leukemia. On one hand, the invention provides an application of composition containing pyridyl pyrilamine compounds in preparation of the drug for treating the leukemia; on the other hand, the invention provides an application of composition containing phenyl aminoformylthiazole compounds in preparation of the drug for treating the leukemia; and the invention provides an application of quinoline compounds in preparation of the drug for treating the leukemia.

Prostate cancer and hematological neoplasms are treated by administration of (i) a compound of Formula I: wherein: R1 is —OH or —O—P(O)(OH)2; and R2 is (II) or (III); (ii) N6-benzyladenosine, (iii) N-(phenylmethyl)-7-β-D-ribofuranosyl-7H-pyrrolo [2,3 -d]pyrimidin-4-amine, (iv) N-(phenylmethyl)-7β-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 5′-monophosphate; or a pharmaceutically acceptable salt thereof.

A Preparation method of pyrazolo[3,4-d]pyrilamine compounds comprises the following steps: allowing phosphinimine prepared by pyrazole compounds with cyans and aminos at an ortho-position to react with various isocyanates by an aza-witting reaction under a mild condition in dichloromethane to obtain carbodiimide, then performing a cyclization reaction with alcohol in solvent alcohol with sodium hydroxide as an alkali so as to efficiently prepare the pyrazolo[3,4-d]pyrilamine compounds through a series process. The method of the invention is mild in reaction condition, wide in substrate application scope (R1=H or various electron-donating groups such as CH3, OCH3, OC2H5, and the like, or various electron-withdrawing groups such as 4-Cl, 4-F, and the like, wherein R2 is methanol or ethanol), less in side reaction, high in product purity, and convenient for separation and purification; the method is convenient for operation, low in cost, suitable for large-scale preparation, and has very good application prospects.