Disclosed are a new crystal form of a rosuvastatin calcium intermediate, [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonamido)-5-pyrimidyl]triphenylphosphonium bromide, and a preparation method therefor. The XRPD spectrum of the crystal form, which is measured by using CuKα irradiation and is represented by 2θ angles, has diffraction peaks at least at 7.475º ± 0.2º, 8.626º ± 0.2º, 9.414º ± 0.2º, 10.753º ± 0.2º, 11.382º ± 0.2º and 14.940º ± 0.2º. The crystal form has low hygroscopicity and good stability, and is convenient for long-term storage and transportation.
2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases.
wherein; X is N or CH; R is
6 alkyl is optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, and I.
C07C 275/26 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of rings other than six-membered aromatic rings
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 275/04 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
3.
CYCLOHEXANE DERIVATIVE OR STEREOISOMER OR SALT THEREOF, AND PREPARATION AND USE THEREOF
Provided are a cyclohexane derivative as shown by formula IB or a stereoisomer or a salt thereof, and the preparation and use thereof. The cyclohexane derivative has a high affinity for D3 receptors and 5-hydroxytryptamine, has a lower affinity for D2 receptors, shows a high selectivity for D3/D2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases wherein X is N or -CH-; where R group is optionally substituted with one or more substituents selected from halogen and Ci-Ce alkyl; and further where the Ci-Ce alkyl is optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br and I.
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
4.
CYCLOHEXANE DERIVATIVE OR STEREOISOMER OR SALT THEREOF, AND PREPARATION AND USE THEREOF
Provided are a cyclohexane derivative as shown by formula IB or a stereoisomer or a salt thereof, and the preparation and use thereof. The cyclohexane derivative has a high affinity for D3 receptors and 5-hydroxytryptamine, has a lower affinity for D2 receptors, shows a high selectivity for D3/D2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases; and the preparation method thereof is simple and easy.
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
5.
Process for preparing (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate
A process for preparation of (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate (Formula I), comprising reacting (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinoline (Formula II) with carbon dioxide and an alkylating agent R-LG in the presence of a base to obtain the compound of Formula I in an organic solvent.
In Formula I and II, R is an alkyl or a substituted alkyl; LG is a leaving group.
C07D 217/06 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 453/02 - Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Method for preparing cinacalcet hydrochloride having the steps of heating (R)-1-naphthyl ethylamine (Formula I) and 3-(trifluoromethyl)benzene (Formula II)
wherein L is a halogen atom, methanesulfonate group (OMs), p-Toluenesulfonate (OTs), or triflate (OTf), in an organic solvent in presence of an inorganic base, refluxing until 3-(trifluoromethyl)benzene is completely consumed, obtaining a reaction mixture containing cinacalcet, and after treatment, obtaining cinacalcet hydrochloride having a formula of
The post treatment separates (R)-1-naphthyl ethylamine hydrochloride and cinacalcet hydrochloride by adjusting pH value, extraction, and other simple operations, and the (R)-1-naphthyl ethylamine obtained is recycled for preparing the next batch of cinacalcet hydrochloride.
C07C 209/02 - Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of hydrogen atoms by amino groups
C07C 209/16 - Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
C07C 209/08 - Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
7.
TICAGRELOR MONOHYDRATE, PREPARATION METHOD THEREFOR AND USE THEREOF IN PHARMACY
Disclosed is a ticagrelor monohydrate crystal form. There are two large endothermic peaks at 102±5°C and 136±5°C in the differential scanning calorimetry spectrum thereof, and the thermogravimetry spectrum displays the presence of one molecule of crystallization water. This crystal form has a good storage stability, and the water-solubility thereof is better than the anhydrous crystal form reported. The ticagrelor monohydrate is obtained by heating and dissolving ticagrelor in a mixed solvent of an organic solvent and water, then cooling, crystallizing, filtering, and drying it. The preparation method is easy to operate, the solvent thereof is environmentally friendly and controllable and thus is easy to recycle and reuse, therefore the method is suitable for industrial mass production. The ticagrelor monohydrate can be used for preparing drugs for treating/preventing thrombosis.
Provided is a preparation method of (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline carboxylate (the compound of formula I), the method comprising reacting (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline (the compound of formula II) with carbon dioxide and alkylating agent R-LG in organic solvent, and the reaction equation is shown as formula (III), wherein R is an aliphatic alkyl or a substituted aliphatic alkyl, and LG is a leaving group.
C07D 217/06 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 453/02 - Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
The present invention provides a method of preparing cinacalcet hydrochloride. With the presence of inorganic alkali, heat and reflux (R)-1-Naphthylethylamin (Formula I compound ) and m-trifuoromethyl phenyl compound (Formula II compound) in an organic solvent till Formula II compound disappears, so as to obtain a cinacalcet reaction mixture. Obtain cinacalcet hydrochloride through post-processing. In Formula II, L is a halogen atom, trifluoromethanesulfonat (OMs), tosylate (OTs), and methanesulfonat (OTf). The present invention In the post-processing, (R)-1-Naphthylethylamin hydrochloride and cinacalcet hydrochloride are separated through simple operations such as pH control and extraction. (R)-1-Naphthylethylamin extracted and separated can be recycled and used to prepare a next batch of cinacalcet hydrochloride. For the present invention, the operations are simple, the post-processing is convenient, the yield is high, related substances in the prepared cinacalcet hydrochloride are low in content, and the quality is high. The method of present invention is suitable for industrial production and has a high application value.
C07C 209/08 - Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
C07C 209/16 - Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
C07C 211/30 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
patents
