123 results about "Azabicyclane" patented technology

The present invention relates to substantially crystalline and solid state forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide (Form A-HCl, Form B, Form B-HCl, or any combination of these forms), pharmaceutical compositions thereof, and methods of treatment therewith.

The present invention relates to processes for preparing solid state forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide, including Compound 1 Form A, Compound 1 Form A-HCl, Compound 1 Form B, and Compound 1 Form B-HCl, any combination of these forms, pharmaceutical compositions thereof, and methods of treatment therewith.

The invention provides a method for preparing cefoxitin sodium, which comprises the following steps: 1, using deacetyl7-ACA as a raw material, and introducing thiopheneacetyls to obtain an deacetylthiophene acid I; 2, introducing carbamoymethoxyls to the positions 3 of molecules of deacetylthiophene acid I to obtain an intermediate of (6R, 7S)-3-carbamoymethoxyl-7-[2-(2-theiophene) acetamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]octa-2-en-2-methanoic acid II; 3, reacting the intermediate II with lithium methoxide to introduce methoxyls into positions 7 of the molecules of the intermediate to obtain cefoxitin acid III; and 4, adding ethanol solution of a sodium salt into an organic solvent containing the cefoxitin acid and obtaining the cefoxitin sodium IV through suction filtration and drying.

The present invention relates to novel 3-azabicyclo[3.1.0]hexane derivatives as dipeptidyl peptidase-IV inhibitors and the processes for the synthesis of the said compounds. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating diabetes, especially type 2 diabetes, as well as prediabetes, diabetic dyslipidemia, metabolic acidosis, ketosis, satiety disorders, and obesity. These inhibitors can also be used to treat conditions manifested by a variety of metabolic, neurological, anti-inflammatory, and autoimmune disorders like inflammatory disease, multiple sclerosis, rheumatoid arthritis; viral, cancer and gastrointestinal disorders. The compounds of this invention can also be used for treatment of infertility arising due to polycystic ovary syndrome.

The invention provides novel compositions and methods of making (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and other 1-aryl-3-azabicyclo[3.1.0]hexanes, including synthetic methods that form novel intermediate compounds of the invention for producing)-(−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and other 1-aryl-3-azabicyclo[3.1.0]hexanes and pharmaceutically acceptable salts thereof.

The invention provides 8-azabicyclo[3.2.1]octyl-2-hydroxybenzamide compounds of formula (I):

wherein R², R⁷, and m are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Disclosed is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, A represents a group that is represented by formula (A-1); R1a and R1b may be the same or different and each independently represents a C1-6 alkyl group which may be substituted by one to three halogen atoms; m and n each independently represents an integer of 0-5; X1 represents a hydroxyl group or an aminocarbonyl group; Z1 represents a single bond or the like; and R2 represents an optionally substituted C1-6 alkyl group, an optionally substituted C6-10 aryl group or the like.)

The invention relates to the technical field of drug intermediates, in particular to a synthesis method of 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane, 6, 6-dimethyl-3-oxazolo [3.1. 0] hexane-2-ketone is used as a raw material, the 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane is prepared through hydrolysis, oxidation, dehydration, ammonolysis cyclization and reduction, the 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane is used as a raw material, and the 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane is used as a raw material for preparing the 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane. The synthesis method comprises the following steps of: synthesizing 6, 6-dimethyl-3-oxazole ring [3.1. 0] hexane-2-ketone as a compound as shown in a formula, and 6, 6-dimethyl-3-azabicyclo [3.1. 0] hexane as a compound as shown in a formula in the specification according to a specific synthesis route as follows: synthesizing 6, 6-dimethyl-3-oxazole ring [3.1. 0] hexane-2-ketone as shown in a formula in the specification; the method has the advantages that starting materials are cheap and easy to obtain, the obtained key intermediate is cis-form and can be subjected to ring closing at room temperature, 200-DEG C high-temperature conditions are avoided, post-treatment of the intermediate is simple, pollution of three wastes is less, energy consumption is low, environment cost is low, and the method is suitable for industrial production.

Belonging to the technical field of drug intermediate purification, the invention discloses a purification method of 3-azabicyclo-octane hydrochloride. The process includes: adding potassium borohydride and anhydrous zinc chloride into a mixed solvent of dried toluene and tetrahydrofuran at room temperature, mixing them, conducting nitrogen protection, inputting quantified 1, 2-cyclopentyl dicarboximide in batches, carrying out nitrogen protection and mixing, slow raising the temperature to 70-75DEG C, performing thermal preservation reaction for 4h, slowly raising the temperature to 95-105DEG C and performing thermal preservation reflux reaction for 10h to achieve complete reaction, distilling off some organic solvents, then implementing cooling to 30DEG C, slowly adding liquid alkali to pH of 13-14, conducting steam distillation till fraction pH of 7-8, extracting the fraction with an organic solvent for 3-5 times, acidifying the organic solvent layer with refined hydrochloric acid to pH of 1.5-2, carrying out heating backflow to remove water in the organic layer, and performing cooling suction filtration to obtain an azabicyclo solid crude product. The crude product is refined by a mixed solvent of alcohol and ester, thus obtaining the fine azabicyclo solid. The method provided in the invention has the characteristics that the production process is improved, the purity and yield of the target product are enhanced, and the production cost is reduced at the same time.

The invention belongs to the technical field of medicine. The invention discloses a raw material of cephalosporins and a preparation method thereof. The raw material contains (6R,7S)-7-[2-[(S)-2-amino-2-carboxyethyl Thio]acetylamino]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1- Sodium azabicyclo[4.2.0]oct-2-ene-2-carboxylate heptahydrate, content greater than or equal to 99.6% less than 100%; containing 7-[2-[2-amino-2-carboxyethylthio] Acetylamino]-7-methylthio-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] Oct-2-ene-2-carboxylic acid or 7-[2-[2-amino-2-carboxyethylthio]acetamido]-7-methylthio-3-[[(1- Sodium methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, The content is greater than 0 and less than or equal to 0.3%.

A method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis(aryl) carbonate to form (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline of formula (V) in an inert atmosphere to form a Solifenacin base, which is converted into its pharmaceutically acceptable salts. The invention also provides a compound, (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa), which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.

The invention relates to a (6R, 7R)-3-[(acetyloxy) methyl]-7-[alpha-(N, N'-dicyclohexyl amidine thio)-acetylamino]-8-oxo-5-thia-1-azabicyclo [4, 2, 0]-oct-2-ene-2-carboxylic acid, a crystal thereof, and a preparation method and application thereof. Under alkaline conditions, 7-ACA reacts with bromoacetyl bromide to obtain a 7-bromo acetamino-3-[(acetyloxy) methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2 formic acid intermediate A; and the intermediate A reacts with N, N '- dicyclohexyl thiourea to obtain the compound provided by the invention. The compound is further refined to obtain the crystal with high purity and good stability of the compound provided by the invention. The compound and the crystal thereof have antibacterial effect on Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis, and are potential antimicrobial drugs with promising application prospect.

The invention discloses a synthesis method of a ramipril key intermediate. The ramipril key intermediate is 2-azabicyalo [3.3.0] octane-3-carboxylic acid hydrochloride. The 2-azabicyalo [3.3.0] octane-3-carboxylic acid hydrochloride is obtained through sequential dehydration cyclization, formaldehyde condensation, hydrolysis, removal, Michael addition, cyclization and palladium-carbon catalytic hydrogenation reduction of N-benzoyl-glycine as a raw material. According to the synthesis method of the ramipril key intermediate, the required raw material and reagent are cheap and available, the yield is relatively high, the operation is simple, the cost is low and the method is suitable for industrial production.

The invention relates to a 6-azabicyclo (3.2.1) nonane-3-substituted derivative and a preparation method thereof, which mainly solve the technical problems that the extension of the prior endocyclic compound with 6-azabicyclo (3.23.1) nonane structure in a space structure is limited and the water solubility of the compound is poor. The reaction formula of the 6-azabicyclo (3.2.1) nonane-3-substituted derivative is shown as above. 3-nitrile-6-azabicyclo (3.2.1) nonane compound IV is obtained by adopting 6-azabicyclo (3.2.1) nonane-3-ketone III as raw materials through nitrile addition, and then the compound IV is reacted with ethanol under acid condition to generate ester compound I; or the compound III is reacted with oxyammonia, aminos, hydrazines, amides, sulfonamides, hydrazides or sulfonyl hydrazides to generate compound V, and the compound V is reduced to generate compound II.

The invention discloses a simple and convenient preparation method of relebactam. According to the method, a key intermediate (2S,5R)-5-benzyloxyamino piperidine-2-formic acid is prepared by using (S)-N-protective group-5-oxo-2-piperidinecarboxylic acid or a salt form thereof as an initial raw material; the (2S,5R)-5-benzyloxyamino piperidine-2-formic acid and phosgene, solid phosgene or diphosgene are subjected to acylating chlorination, cyclic ureation, and reaction with 1-protective group-4-aminopiperidine to obtain (2S,5R)-6-benzyloxy-N-(1-protective group-4-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide; and debenzylation, sulfonyl oxidation, ammonium salt formation and deprotection are performed to prepare relebactam. According to the invention, the raw materials are cheap, easyto obtain and low in cost, the technological process is safe, simple and convenient to operate, small in wastewater and waste salt yield and environmentally friendly, the reaction atom economy is high, the reaction selectivity of each step is high, the purity and the yield are high, and industrial production is facilitated.

The present disclosure is directed to solid forms of the compound of formula (I):

to compositions comprising these forms, and to processes for their preparation. The disclosure also relates to methods for the treatment of neurological disorders through the administration of these forms.