- Discovery of novel substituted octahydropyrrolo[3,4-c]pyrroles as dual orexin receptor antagonists for insomnia treatment
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A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency.
- Wu, Songliang,Sun, Yu,Hu, Yi,Zhang, Hongmei,Hou, Lijuan,Liu, Xing,Li, Yufeng,He, Haiying,Luo, Zhi,Chen, Yuan,Wang, Yuhe,Shi, Weihua,Shen, Liang,Cao, Changqing,Liang, Wei,Xu, Qing,Lv, Qiang,Lan, Jiong,Li, Jian,Chen, Shuhui
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Read Online
- Preparation method of moxifloxacin intermediate
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The invention discloses a preparation method of a moxifloxacin intermediate. The invention provides a preparation method of a compound as shown in a formula III, which comprises the following step: ina solvent, in the presence of alkali, carrying out cyclization reaction as shown in the specification on a compound as shown in a formula II to obtain the compound as shown in the formula III. The method is simple to operate, high in chiral selectivity, simple in process, high in yield and high in purity.
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- Catalytic Transfer Hydrodebenzylation with Low Palladium Loading
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A highly-efficient catalytic system for hydrodebenzylation reaction is described. The cleavage of O-benzyl and N-benzyl protecting groups was performed using an uncommonly low palladium loading (0.02–0.3 mol%; TON up to 5000) in a relatively short reaction time. The approach was used for a variety of substrates including pharmaceutically important precursors, and gram-scale deprotection reaction was shown. Transfer conditions together with easy-to-make Pd/C catalyst are the key features of this debenzylation scheme. (Figure presented.).
- Yakukhnov, Sergey A.,Ananikov, Valentine P.
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p. 4781 - 4789
(2019/09/16)
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- Tri(pentaflurophenyl)borane-catalyzed reduction of cyclic imides with hydrosilanes: Synthesis of pyrrolidines
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B(C6F5)3-catalyzed hydrosilylation of cyclic imides afforded an efficient synthetic method of pyrrolidines. In the presence of 5 mol% B(C6F5)3, various aromatic, aliphatic and polycyclic imides were smoothly reduced by PhSiH3 to generate the corresponding pyrrolidines in high yields. The reaction profiles monitored by 1H NMR spectroscopy disclosed the reduction process of cyclic imides and the effect of difference structure of the hydrosilanes on the hydrosilylation.
- Ding, Guangni,Wu, Xiaoyu,Lu, Bin,Lu, Wenkui,Zhang, Zhaoguo,Xie, Xiaomin
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p. 1144 - 1150
(2018/02/17)
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- Pyrrolidines compound and its synthesis method (by machine translation)
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A pyrrolidine compound and its synthetic method, will be dissolved in an organic solvent in the cyclic imide compound with hydrogen as a reducing agent of the reagent and a Lewis acid as a catalyst mixing, under the condition of refluxing to prepare the aromatic ring and fat ring pyrrolidines. Synthetic route of this invention is simple, efficient and economic, mild condition, wide applicability, to pyrrolidines compound at the later stage of industrial production will play a great role in promoting. (by machine translation)
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Paragraph 0020; 0021; 0034; 0035; 0036
(2017/08/28)
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- Moxifloxacin intermediate compound preparation method
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The invention discloses a preparation method of a moxifloxacin intermediate compound. The invention discloses a preparation method of a moxifloxacin intermediate compound represented by the formula B which is shown in the description. The preparation meth
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Paragraph 0032; 0033
(2017/08/25)
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- A 3 - amino-pyrrolidine compound and its synthesis and use
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The invention relates to 3-aminopyrrolidine compounds, and a synthetic method and uses thereof. 3-pyrrolidone compounds (compounds IIIa or IIIb) are adopted as substrates and subjected to transaminase reactions under the actions of transaminase and an amino donator to obtain the (S)-3-aminopyrrolidine compounds (compounds II). Then intramolecular cyclization and removal of amino protective groups are performed to obtain (S,S)-2,8-diazabicyclo[4,3,0] nonane (a compound I). According to the 3-aminopyrrolidine compounds, the synthetic method and the uses, a synthetic technology that is low in cost, short in process steps and environmental friendly is provided for a moxifloxacin intermediate, and the synthetic technology will have great market application value and is suitable for large-scale industrial production.
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Paragraph 0053; 0054; 0057
(2018/10/19)
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- Efficient synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane
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An efficient synthetic route for moxifloxacin chiral intermediate via five steps was established. First, dehydration, N-acylation, and cyclization were combined in one pot to meet the industrial requirement. Then relatively low hydrogen pressure was employed in the catalytic hydrogenation reaction with high yield. Isopropanol/water system was used in resolution, which guaranteed high yield and perfect optical purity. The racemic process conducted by manganese dioxide and Pd/C successfully converted the undesired enantiomer into the racemate and hence the total yield increased remarkably. Furthermore, mild hydrogen transfer catalytic hydrogenation method was utilized in debenzylation process instead of high-pressure hydrogenation. Total yield of 39.0% was achieved, which was much higher than that of 29.0% in literature.
- Chen, Shipeng,Liu, Dongqi,Si, Leilei,Chen, Ligong,Yan, Xilong
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p. 238 - 244
(2017/01/22)
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- (S, S) - 2,8-diazabicyclo [4.3.0] nonane preparation method
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The invention relates to a novel preparation method of (S,S)-2,8-diazabicyclo[4.3.0]. The method comprises the steps that: 2,3-pyridine dicarboxylic acid derivative and amide are subjected to condensation, such that 2,3-pyridine dicarboximide is formed; 2,3-pyridine dicarboximide is subjected to protection and hydrogenation reduction, such that 8-substituted-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane is produced; the product is reduced in a borohydride reduction system, such that 8-substituted-2,8-diazabicyclo[4.3.0]nonane is obtained; the product is subjected to optical-active organic acid resolution, such that 8-site protection group is removed, and the final product is obtained. Or, 2,3-pyridine dicarboximide is directly subjected to hydrogenation reduction, such that 7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane is produced; the product is directly reduced in a borohydride reduction system, such that 2,8-diazabicyclo[4.3.0]nonane is produced; the 2,8-diazabicyclo[4.3.0]nonane is subjected to optical-active organic acid resolution, such that the final product is directly obtained. The method provided by the invention is advantaged in simple reaction route. The raw materials are cheap and easy to obtain. The reaction conditions are mild and easy to control. The method is suitable for industrialized productions.
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- Preparation method for 8-benzyl-2,8-diazabicyclo[4.3.0]-nonane
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The invention discloses a preparation method for 8-benzyl-2,8-diazabicyclo[4.3.0]-nonane (II). According to the preparation method, N-benzyl pyrrole ketone ester (XIV) is taken as raw materials to react with acrylonitrile in organic solvent on the condition that a catalytic amount of alkali carbonate exists to obtain a compound (XV), the compound (XV) is processed through hydrolyzing decarboxylation to obtain a compound (XVI), and the compound (XVI) is subjected to a catalytic hydrogenation and reductive cyclization reaction to obtain the objective product 8-benzyl-2,8-diazabicyclo[4.3.0]-nonane (II). The preparation method mainly has the advantages that the whole process is simple, the reaction condition is mild, the process is safe, the yield is high, the product quality is high, and industrialized production is facilitated.
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- Synthesis method for moxifloxacin side chain
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The invention discloses a synthesis method for a moxifloxacin side chain.With 2,3-dipicolinic acid being a raw material, cyclization, catalytic hydrogenation, resolution and racemization are performed, and then chemical reduction and debenzylation are performed to obtain moxifloxacin side chain.Resolution, racemization and chemical reduction are performed in sequence, sodium borohydride is used for replacing high-risk lithium aluminum hydride to synthesize the moxifloxacin side chain, and the synthesis method has the advantages that industrial waste materials are reduced, the production cost is lowered, and productivity is increased.
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- (S, S) - 2,8-diazabicyclo [4, 3, 0] nonane synthetic method
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The invention discloses a preparation method of a compound 1 (S,S)-2,8-diazabicyclo[4.3.0]nonane. With existing methods, chiral separations are carried out in the last process, and chiral control are not realized in pre-stage main ring synthesis process, such that a final total yield is substantially low, and synthesizing cost of (S,S)-2,8-diazabicyclo[4.3.0]nonane is severely influenced. According to the method provided by the invention, in an organic solvent, under the existence of organic amine and under a temperature of 0-30 DEG C, benzenesulfonamide is subjected to a reaction with acrolein, such that a compound 5 is prepared; under the existence of organic amine and a chiral catalyst, the compound 5 is subjected to a D-A addition reaction with a compound 4, such that a compound 6 is prepared; the compound 6 is processed through catalytic hydrogenation and carbonyl reduction; and protective group removing and chiral separation purification are carried out under an acidic condition. With the method provided by the invention, a problem of low total yield of finished product caused by chiral separation of prior arts is completely solved, and product yield is improved.
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Paragraph 0035-0040; 0042-0043
(2017/03/08)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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- METHOD FOR PRODUCTION OF (S,S)-6-BENZYLOCTAHYDRO-1H-PYRROLO[3,4-B]PYRIDINE, AN INTERMEDIATE OF AZABICYCLO PYRIDINE DERIVATIVES
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The present invention relates to a cost effective process for the production of (S,S)-6- benzyloctahydro-1H-pyrrolo[3,4-b]pyridine of Formula (I), an important intermediate for the manufacture of azabicyclo pyridine derivatives.
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- IR, FT-ICR-MS studies on (1′S, 6′S)-1-cyclopropyl-7-(2,8- diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid hydrochloride salt
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The infrared spectra of (1′S, 6′S)-1-cyclopropyl-7-(2,8- diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid hydrochloride salt (CLF-HCl) were studied and compared with free base. Their fragmentation pathways were investigated using tandem mass spectrometric (MS/MS) techniques on Fourier-transform ion cyclotron resonance spectrum, and many characteristic fragment ions were found.
- Lin, Zhiwei
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p. 254 - 258
(2013/12/04)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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- A novel synthesis of (4aS,7aS)-Octahydro-1H-pyrrolo[3,4-b]pyridine:An intermediate of Moxifloxacin Hydrochloride
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A novel synthesis of (4aS, 7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine (1) is demonstrated alongwith recovery and reuse of chiral auxiliary naproxen. Further to this alternative stereoselective reduction procedures on 6-benzyl-5H- pyrrolo[3,4-b]pyridine-5,7(6H)-dione 3 enabling the desired chirality in the nonane 1 is demonstrated.
- Reddy, G. Prashanth,Bandichhor, Rakeshwar
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p. 8701 - 8707
(2013/11/06)
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- Racemisation of (1R, 6S)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane using halogenated solvent in basic medium
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A simple, highly rapid, efficient and eco friendly process for Racemisation of (1R, 6S)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0] nonane in various halogenated solvents has been carried out as a base catalysed reaction to afford racemic mixture in excellent yields (80-95%) at temperature of or below 40°C. The base catalysed racemisation in halogenated solvent has an advantage of simple workup procedure, and use of less volume of halogenated solvent irrespective of type of solvent used in the reaction system.
- Bhavsar, Jigar,Bhashkar, Bhuwan,Kumar, Anil
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p. 241 - 246
(2013/06/27)
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- A PROCESS FOR PREPARATION OF INTERMEDIATE OF MOXIFLOXACIN
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The present invention provides a process for the preparation of racemic or chiral octahydro-6-(phenylmethyl)-1H-pyrrolo[3,4-b]pyridine of formula I, a key intermediate in the synthesis of moxifloxacin or its pharmaceutically acceptable salts. The process
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Page/Page column 10; 14-15
(2012/10/18)
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- SYNTHESIS OF (4aS,7aS)-OCTAHYDRO-1H-PYRROLO[3,4-b]PYRIDINE
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The present invention relates to the stereoselective synthesis of (4aS,7aS)-octahydro-1H-pyrrolo [3, 4-b]pyridine, as well as the conversion thereof, to give Moxifloxacin. Particularly, the present invention relates to a method for the synthesis of (4aS,7aS)-octahydro-1H-pyrrolo[3, 4-b]pyridine of formula (I) comprising : (a) the optical resolution by enzymatic hydrolysis of the intermediate dialkyl-1-alkylcarbonylpiperidine-2,3-dicarboxylate racemate of formula (II) to give, following isolation, the intermediate dialkyl-(2S,3R)-1-alkylcarbonyl-piperidine-2,3-dicarboxylate of formula (III) in which AIk is a straight or branched C1-C5 alkyl group; (b) the conversion of the intermediate (III) to (4aR,7aS)-1-alkylcarbonylhexahydrofuro[3, 4-b]pyridine-5,7-dione of formula (IV) in which AIk has the meanings set forth above; (c) the conversion of the intermediate (IV) to (4aS,7as)-octahydro-1H-pyrrolo[3, 4-b]pyridine of formula (I) with an optical purity above 99%.
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Page/Page column 36
(2010/09/18)
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- IMPROVED PROCESS FOR THE PREPARATION OF (S.S)-2.8-DIAZABICYCLO[4.3.0]NONANE
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The present invention is directed to an improved industrially viable, cost effective process for manufacturing (S,S)-2,8-Diazabicyclo[4.3.0]nonane in a substantially pure form and consequent conversion to Moxifloxacin hydrochloride monohydrate.
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Page/Page column 6; 10
(2009/11/29)
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- PHENYLAMINOPYRIMIDINES AND THEIR USE AS RHO-KINASE INHIBITORS
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The invention relates to the phenylaminopyrimidines of formula (I), wherein A, D, R1, R2, R3 and R4 are defined as in the description. The invention also relates to methods for producing said phenylaminopyrimidines and to their use for producing drugs for the treatment and/or the prophylaxis of diseases, especially cardiovascular diseases.
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Page column 55,56
(2010/02/06)
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- Bicyclic amine derivatives
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A compound represented by formula (I) or a salt thereof: STR1 wherein X1 and X2 each represent a halogen atom; R1 represents a hydrogen atom or a substituent; R2 represents a substituted or unsubstituted bicyclic heterocyclic substituent of the following formula; STR2 wherein R3, R4, Y, Z, m, n, p, q and r are as defined herein; A represents a nitrogen atom or a substituted carbon atom; and R represents a hydrogen atom or a substituent. The compound exhibits potent antimicrobial activity and also high safety due to reduced lipophilicity.
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- Quinolonecarboxylic acids
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The invention relates to novel derivatives of quinolonecarboxylic acid and naphthyridonecarboxylic acid which are linked to a β-lactam antibiotic, to their salts, to processes for their preparation and to antibacterial agents containing these derivatives.
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- 8-vinyl- and 9-ethinyl-quinolone-carboxylic acids
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The invention relates to new 8-vinyl- and 8-ethinylquinolonecarboxylic acids, process for their preparation, and antibacterial agents and feed additives containing them.
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- 7-(1-PYRROLIDINYL)-3-QUINOLONE-AND-NAPHTHYRIDONECARBOXYLIC ACID DERIVATIVES AS ANTIBACTERIAL AGENTS AND FEED ADDITIVES
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7-(1-Pyrrolidinyl)-3-quinolone- and -naphthyridonecarboxylic acid derivatives as antibacterial agents and feed additives, of the formula in which X1 is halogen, X2 is hydrogen, halogen, amino or other radical, R1 is alkyl, cycloalkyl, optionally substituted phenyl or other radical, R2 is hydrogen, alkyl or a dioxolylmethyl radical, R 3 i s A is N, CH, C-halogen, or the like, or forms a bridge with R1, and addition products thereof
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