64 results about "Dihydropyran" patented technology

The invention provides an engineered ketoreductase mutant, which comprises a polypeptide sequence, a gene sequence, a recombinant expression vector containing the gene, an engineering strain, a protein expression method of the engineering strain, and a reaction process for selectively synthesizing (R)-5, 7-difluorochroman-4-ol by using the engineered ketoreductase mutant.

This disclosure provides compounds of Formula ( AA ) Formula ( A ), Formula ( I ) (e.g., Formula ( I-a1 )), Formula ( II ) (e.g., Formula ( II-1 ), ( II-a ), ( II-a1 ), ( II-a2 ), or ( II-a3 )), Formula ( III ) (e.g., Formula ( III-1 )), Formula ( IV ) (e.g., Formula ( IV-a ), ( IV-a1 ), ( IV-b ), ( IV-b1 ), or ( IV-c )), or Formula ( B ) (e.g., Formula ( B-1 )), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein. In some embodiments, the KRas protein has a dysregulation (e.g., the KRas protein is mutated or amplified). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) KRas activation, for example, KRas activation associated with a mutant KRas protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds as disclosed herein, or pharmaceutically acceptable salts thereof, and methods of using and making the same.

The invention discloses a fesoterodine intermediate preparation method, and belongs to the technical field of chemical medicine raw material medicine synthesis, 6-(hydroxymethyl)-4-phenylchroman-2-ol and diisopropylamine are used as starting materials to prepare a fesoterodine intermediate, an inert conversion reagent is used, and the reaction temperature is controlled to be 30-60 DEG C, so that the fesoterodine intermediate is obtained. On the other hand, the excessive diisopropylamine reacts with an inert conversion reagent, the excessive diisopropylamine is converted into an excessive state which does not react with the product, and the excessive diisopropylamine is prevented from reacting with the product to generate a large amount of various impurities; a reducing agent and an inert conversion reagent are introduced to be combined, so that the problem of impurity generation caused by palladium catalytic hydrogenation reduction is avoided.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The invention discloses a preparation method of a cresol trozole trisiloxane intermediate, and belongs to the technical field of fine chemical engineering. The preparation method comprises the following steps: by taking 2, 6-dibromo-4-methylphenol as a raw material, reacting with 3, 4-dihydropyran under the action of p-toluenesulfonic acid, so as to generate an intermediate 2-(2, 6-dibromo-4-methylphenoxy) pyran; reacting with sodium methoxide under the action of a catalyst to generate an intermediate 2-(2-bromo-4-methyl-6-methoxyphenoxy) pyran; then generating a Grignard reagent, carrying out coupling reaction on the Grignard reagent and 3-bromine-2-methallyl, finally reacting with benzotriazole lithium salt, and carrying out acidolysis deprotection to obtain the cresol trozole trisiloxane intermediate. The raw materials are available in the market, the overall yield is high, and a route reference is provided for synthesis of the compounds.

The application discloses a preparation method of 3,4-dihydropyran derivatives, and a reaction formula is as follows: the unactivated propenal and the weak polar olefin which are simple in structure and low in material cost are used as starting materials, the unactivated propenal and the weak polar olefin which are weak in reactivity can participate in [4+2] cycloaddition, and the 3,4-dihydropyran derivatives with high purity can be prepared; the preparation process is simple in operation, high in yield and excellent in diastereoselectivity, can effectively convert low-cost raw materials into high-value-added compounds, and provides an economic and efficient synthesis strategy for related industries.

Derivatives of Sabinene (1-isopropyl-4-methylenebicyclo[3.1.0]hexane, CAS No. 3387-41-5), as well as their synthesis and use in organoleptic applications, are described herein. The Sabinene derivatives include a compound having a general Formula (I), wherein --- is a single or a double bond; wherein if --- is a single bond, then Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5; wherein if --- is a double bond, then Y is O, N-OMe, or N-OEt; R is selected from the group consisting of H, C(O)-R6, and CH(R6)-OR5; R1 is selected from the group consisting of 1,3-dioxepan, 5-methyl-1,3-dioxolan-4-one, (CH=CH)x(CH2)nOH, (CH=CH)x(CH2)nCHO, CH(CH3)CO2Et, and CH(CH3)OH; R2 = H or Me; R3 is selected from the group consisting of CHO, CO2Et, (CH2)nOH, (CH2)nCHO, (CH2)nCN, and (CH2)nCO2Bu; and R4 is CHO or CH2OH; or R3 and R4 in combination form a dihydropyran, a tetrahydropyran, a tetrahydropyranol, a tetrahydropyranone, a dimethylcyclohexenone, or a dimethylcyclohexenol; R5 is selected from the group consisting of CH(CH3), CH(CH2CH3), C(CH3)CH3, and C(CH3)CH2CH3; R6 is selected from the group consisting of OMe and Me; x is an integer selected from 0 or 1; and n is an integer selected from 2 to 7; with the proviso that when --- is a double bond and Y is O, then R and R6 are not H.

The application relates to a catalyst for preparing 3,4-dihydro-2H-pyran, a preparation method of the catalyst and a method for preparing 3,4-dihydro-2H-pyran by using the catalyst. The catalyst comprises a carrier, an active component and a promoter component, and is prepared by immersing the carrier in an active component precursor aqueous solution, stirring and uniformly standing, and then drying; calcining in an air atmosphere; reducing in a hydrogen atmosphere; immersing in a promoter component precursor aqueous solution, stirring and uniformly standing, and then drying; calcining in an air atmosphere; and reducing in a hydrogen atmosphere. The catalyst according to the application is applied to a process for preparing 3,4-dihydro-2H-pyran by taking tetrahydrofurfuryl alcohol as a raw material, the generation of a tetrahydropyran byproduct is reduced, the selectivity of 3,4-dihydro-2H-pyran is improved, and the difficulty of separation is reduced. The method for preparing 3,4-dihydro-2H-pyran provided by the application has the advantages of easy raw material, a more green route, simple process, high efficiency and continuous production.

The invention provides a method for catalytically synthesizing 7-amino-3-oxabicyclo [3.3. 1] nonyl-6-ene-1-ol by using rare earth, which comprises the following steps of: adding a catalyst and a catalyst, according to the preparation method, rare earth trifluoromethanesulfonate is taken as a catalyst, 6-alkoxy-2, 6-dihydropyran-3-ketone and enamine compounds are taken as raw materials, and the 7-amino-3-oxabicyclo [3.3. 1] nonyl-6-ene-1-ol is prepared by catalyzing (3 + 3) cyclization reaction. The synthesis method provided by the invention is simple in reaction raw material synthesis, low in rare earth salt price, easy in experimental operation and suitable for large-scale preparation. The obtained compound can be applied to the fields of organic synthesis, drug synthesis, organic materials and the like.

The present invention relates to novel crystalline forms of (S)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide, processes for their preparation, medicaments, and pharmaceutical compositions containing these forms.

The present invention belongs to the field of organic synthesis and specifically relates to a method for synthesizing 2'-fluoro-2'-deoxyuridine and its intermediates. The method comprises the following steps: The method prepares 2'-fluoro-2'-deoxyuridine by constructing novel intermediates, namely, compounds of formula IV, III, and II. This method avoids the use of reagents such as dihydropyran, which are strong eye and skin irritants. The method results in milder reaction conditions, lower costs, simple operation, environmental friendliness, high yield, and suitability for industrial production.

The invention provides a method for catalytically synthesizing 7-oxa-2-azabicyclo [3.3. 1] nonyl-3-ene-1-ol by using rare earth, which comprises the following steps of: adding a catalyst and a catalyst, according to the preparation method of the 7-oxa-2-azabicyclo [3.3. 1] nonyl-3-ene-1-ol, rare earth trifluoromethanesulfonate is taken as a catalyst, 6-alkoxy-2, 6-dihydropyran-3-ketone and enamine compounds are taken as raw materials, and the preparation of the 7-oxa-2-azabicyclo [3.3. 1] nonyl-3-ene-1-ol is realized. The method is simple in reaction raw material synthesis, simple in experimental operation and suitable for large-scale preparation. The obtained compound can be applied to the fields of organic synthesis, drug synthesis and the like.

This disclosure relates to a hair care composition comprising a compound that can covalently bond to hair and an excipient suitable for administration to hair, wherein the compound that can covalently bond to hair is a compound of formula (I), or its tautomers and / or pharmaceutically acceptable salts, where (I), R 1 L1 represents a protecting group that can be hydrolyzed under physiological conditions after application of hydrogen or a hair care composition to the hair, L1, L2 and L3 independently represent a linker group or are absent, and A1, A2 and A3 independently represent a)C1~C 30 Partial, H, hydroxyl, amino, or halogen, or b) C1-C 60 Represents a part or polymer part, and at least one of A1, A2 and A3 is C1-C of group b). 60 It is a part or polymer part, and C1-C of group b) 60 The present invention relates to a hair care composition in which the polymer portion is configured to act as b1) a humectant, a hair beautifying coating, or a primer for adhering dye to hair, and / or b2) a humectant, a hair beautifying coating, or a fragrance for cleavage from the 3,4-dihydro-2H-pyran portion, and L1-A1 and L2-A2 do not represent portions containing an unsaturated CC bond or CN bond at the alpha position to the carbon atoms marked "a" and "b", respectively. [Formula 1] JPEG2026520679000070.jpg29128

The present disclosure provides compounds of formula (A) (e.g., formula (I) (e.g., formula (I-a1), (I-a2), (I-a3), (I-a4), (I-a5), (I-b1), (I-b2), (I-b3), (I-b4), (I-b5), or (I-c1)), formula (II) (e.g., formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), or (II-b2)), formula (III) (e.g., formula (III-1) or (III-2)), which inhibit KRas protein. Provided are compounds of Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), or (IV-b2)), or Formula (V) (e.g., Formula (Va) or (Vb), (V-a1), (Vc), (Vd), (V-b1), (V-a2), or (V-b2)), or Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e)), or a pharmaceutically acceptable salt thereof. These compounds are useful, for example, for treating diseases, disorders, or conditions in which increased and / or sustained KRas activation (e.g., KRas activation associated with a mutant KRas protein) contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition. The present disclosure also provides compositions containing the compounds provided herein or pharmaceutically acceptable salts thereof. TIFF2025541682000773.tif91128

The invention discloses a preparation method of a trifluoromethyl substituted chroman-4-one compound, and relates to the technical field of organic matter synthesis. According to the method, a Togni's reagent is used as a trifluoromethyl source, various 2-allyloxy benzaldehyde compounds are used as substrates, and a nonmetal photosensitizer is used, so that synthesis of various trifluoromethyl substituted chroman-4-ones and derivatives thereof is realized. By optimizing the synergistic effect of the photosensitizer and the light source, substrate limitation is broken through, the reaction stability is improved, and the problems that in the prior art, substrate applicability is limited, light source dependency is high, and the substrate yield is unstable are solved.

The invention discloses a total synthesis method and application of furanose ring pyrrole spiroketal alkaloid, and belongs to the technical field of chemical synthesis and biological medicine. According to the method, D-glucose is used as a raw material and reacts with dibenzylamine, 1-dibenzylamino-1-deoxy-D fructose is prepared through an Amadori rearrangement reaction, 1-amino-1-deoxy-D fructose is prepared through direct hydrogenation debenzylation, or 2-hydroxyl of 1-dibenzylamino-1-deoxy-D fructose is protected by adding methyl and then debenzylation protection is carried out, and 1-amino-1-deoxy-D fructose is obtained. The preparation method comprises the following steps: preparing 1-amino-1-deoxy-2-methoxyl-D-fructose; and respectively carrying out Maillard condensation reaction on the two obtained amino sugars and dihydropyrone, and then completing spiro reaction under an acidic condition to obtain acorine B and pinosine C. The acorine B and pinosine C synthesized by the invention can obviously reduce the weight of an aged mouse, reduce the fat index, reduce lipid droplets in the liver and fat in thymus, reduce the number of aged cells and improve the proportion of T cells in immune cells, and have the potentials of reducing fat and resisting immune aging.

The application discloses a preparation method of a medical intermediate (R)-7-ethyl camptothecin, and relates to the field of chemical medicine synthesis. The application comprises the following contents: (R)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (formula A) and 1-(2-aminophenyl)propan-1-one (formula B) are used as main raw materials, a target compound (R)-7-ethyl camptothecin is obtained through reaction in an organic solvent under the action of a catalyst. The application provides a novel preparation method of the medical intermediate (R)-7-ethyl camptothecin, and the preparation method is simple, stable, high in yield, and suitable for industrial production.

A method for detecting Ag based on phenothiazine + and ClO ‑ The fluorescent probe Tz3 and its preparation method and application relate to the technical field of fluorescent probes. Sodium carbonate is first added to dichloromethane, and then a mixture of 11-ethyl-2-oxo-2,11-dihydropyrano[2,3-b]phenothiazine-3-carbonyl bromide and dimethylpyridinamine is added, followed by stirring at room temperature for reaction. The reaction is completed by TLC detection to obtain the fluorescent probe Tz3. The present invention can distinguish Ag + and Hg 2+ , with good selectivity, anti-interference and sensitivity.

The disclosure provides compounds of Formula (I)or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, CS, R2, and R3 are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The present disclosure provides suspendable ophthalmic solutions with excellent redispersibility. The present disclosure provides an aqueous suspension agent comprising (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide or a pharmaceutically acceptable salt or solvate thereof, a cellulosic polymer, and a nonionic surfactant.

The invention discloses a camptothecin derivative as well as a preparation method and application thereof. The camptothecin derivative has a general formula shown as a structural formula (I). Wherein R1 is one of hydrogen, amino, hydroxyl, methyl, methoxyl, nitryl, halogen and trifluoromethyl, R2 is one of hydrogen, methyl, ethyl and halogen, and R3 is one of hydrogen and acetyl. The preparation method comprises the following steps: carrying out condensation reaction on (S)-4-ethyl-4-hydroxy-7, 8-dihydro-1H-pyran O [3, 4-F] indolizine-3, 6, 10 (4H)-ketone and an o-aminobenzaldehyde / acetophenone derivative in N, N-dimethylformamide under the protection of nitrogen, and synthesizing a target compound through the catalysis of trimethylchlorosilane. The camptothecin derivative prepared by the invention has a remarkable antifungal effect, and tests prove that the camptothecin derivative has broad-spectrum inhibitory activity on various plant pathogenic fungi. According to the invention, the resistance limitation of the traditional bactericide is broken through, and an efficient and low-toxicity novel solution is provided for prevention and treatment of fungal diseases of agricultural and forestry crops.

The application relates to a method for synthesizing dihydropyrrolo[2,3-c]pyrazole analogs. Specifically, under the catalysis of a transition metal and a bidentate ligand, dihydropyrrolo[2,3-c]pyrazole analogs can be obtained in high selectivity by using the bidentate ligand synergy, taking pyrazolinone as raw material and reacting with 1,3-alkyne under the action of triethylenediamine. The application uses cheap and commercially available 1,3-alkyne and easily obtained pyrazolinone, and a series of heterocyclic compounds with potential medicinal value are obtained in high selectivity under simple and mild conditions.

Provided herein are compounds of Formula (IV-b), or pharmaceutically acceptable salts thereof, which inhibit KRas proteins (e.g., modulate aberrant KRas proteins (e.g., mutated or amplified KRas proteins)). The disclosure also provides compositions containing a compound as provided herein, or a pharmaceutically acceptable salt thereof, as well as methods of using and preparing these compositions. Formula (IV-b).

The invention provides a detection method for lure components of a cigarette beetle trap and application of the detection method, and the detection method comprises the following steps: (1) mixing a sample to be detected with an internal standard substance and a solvent for ultrasonic treatment, and then centrifuging to obtain a liquid to be detected; and (2) carrying out gas chromatography-mass spectrometry combined detection on the to-be-detected liquid to obtain the components of the lure of the cigarette beetle trap and the content of the components. The method provided by the invention not only realizes simultaneous separation and determination of antioxidant and killing agent components in the lure of the cigarette beetle trap, but also realizes separation and determination of sex pheromones 4, 6-dimethyl-7-hydroxy-3-nonanone and 2, 6S-diethyl-3, 5S-dimethyl-2, 3-dihydropyran of cigarette beetles, sex pheromones 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z, 9Z The method provided by the invention can be used for simultaneously determining the 4, 6-dimethyl-7-hydroxy-3-nonanone isomeride, especially simultaneously separating the 4, 6-dimethyl-7-hydroxy-3-nonanone isomeride, and is high in chromatographic separation degree, accurate in qualitative analysis and good in quantitative repeatability.

The present disclosure relates to novel sulfate salt forms of 2-(5-methoxyisochroman-1-yl)-4,5-dihydro-1H-imidazole (I). Compound (I) is a selective alpha2A adrenoceptor agonist and is useful in the treatment of anxiety, and for use as a sedative or analgesic agent, and other diseases were alpha2A agonism is desired.

This disclosure provides compounds of Formula ( AA ), Formula ( A ) (e.g., Formula ( I-a1 )), or Formula ( B ), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein. In some embodiments, the KRas protein has a dysregulation (e.g., the KRas protein is mutated or amplified). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) KRas activation, for example, KRas activation associated with a mutant KRas protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula ( AA ), Formula ( A ) (e.g., Formula ( I-a1 )), or Formula ( B ), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The invention provides a pyrrolidone dihydropyrone compound as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. Specifically, under the catalytic action of Lewis base, beta-oxoacrylamide and an alpha-pyrone derivative serve as raw materials, and the pyrrolidone dihydropyrone compound is synthesized through a one-step method. Beta-oxoacrylamide and alpha-pyrone derivatives which are simple and easy to obtain are adopted as starting raw materials, [3 + 2]-cycloaddition reaction is carried out under the catalysis of Lewis base, the pyrrolidone dihydropyrone compound is synthesized, the method is easy and convenient to operate, the reaction condition is mild, the used reagents and raw materials are economical and easy to obtain, and the method is suitable for industrial production. The target product yield is high, and the substrate application range is wide; the compound is applied to preparation of anti-tumor drugs and has a good application prospect.

This disclosure describes an economical and scalable method and process to synthesize the Calcium sensing receptor (CaSR) modulating agent 2-methyl-5-((2R,4S)-2-((((R)-1-(naphthalen-1-yl)ethyl)amino)methyl)chroman-4-yl)benzoic acid, its intermediates and pharmaceutically acceptable salts therefor. Uses of said intermediates for synthesis of compounds which may be intermediates to the synthesis of 2-methyl-5-((2R,4S)-2-((((R)-1-(naphthalen-1-yl)ethyl)amino)methyl)chroman-4-yl)benzoic acid are also described herein.