- Convenient synthesis of (R)-3-[(tert -Butoxycarbonyl)amino]piperidine and (R)-3-[(tert -Butoxycarbonyl)amino]azepane
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(R)-3-[(tert -Butoxycarbonyl)amino]piperidine and (R)-3-[(tert -butoxycarbonyl)amino]azepane were prepared in two steps starting from d -ornithine and d -lysine, respectively. In the key step, N -Boc-protected 3-aminolactams were converted into imido esters by O-alkylation and then hydrogenated to amines, under mild conditions (5 bar H 2, room temperature) and without isolation, over a standard hydrogenation catalyst (5% Pt/C).
- Kadyrov, Renat,Tok, Oleg L.
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p. 3573 - 3577
(2021/07/25)
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- Synthesis method of chiral 3-aminopiperidine and derivatives of 3-aminopiperidine
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The invention relates to a synthesis method of chiral 3-aminopiperidine and derivatives of 3-aminopiperidine. According to the synthesis method, R (or S)-piperidine-3-ethyl formate-L (or D)-tartrate is subjected to a hydrazinolysis reaction after being subjected to benzyl protection, and R or S-1-benzyl-3-aminopiperidine is obtained through azidation and Curtius rearrangement. R or S-1-benzyl-3-aminopiperidine is subjected to debenzylation, R or S-3-aminopiperidine can be obtained, R or S-1-benzyl-3-aminopiperidine is subjected to 3-t-butyloxycarboryl protection and debenzylation in sequence,R or S-(3-t-butyloxycarborylamino) piperidine can be obtained, and corresponding salts of R or S-3-aminopiperidine can be obtained through hydrolyzing deprotection of R or S-(3-t-butyloxycarborylamino) piperidine under the acidic condition. The synthesis method of chiral 3-aminopiperidine and the derivatives of 3-aminopiperidine is low in cost, facilitates industrialization and has high optical purity.
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- Synthetic process of anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride
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The invention relates to a synthetic process of an anti-hyperglycemic drug intermediate R-3-amino-piperidine dihydrochloride. The synthetic process comprises the steps: using inexpensive L-glutamic acid as a starting material, and performing esterification, amino protection, reduction, hydroxyl protection, substitution, cyclization and removal of protecting groups for amino groups so as to obtainthe R-3-amino-piperidine dihydrochloride. Compared with the prior art, the synthetic process has cheap and easily available raw materials, good selectivity, good atomic economy, high total yield and mild reaction conditions, and is suitable for industrial production.
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Paragraph 0068-0071
(2019/11/12)
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- (R)- 3 - Boc - amino piperidine preparation method
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The invention discloses a preparation method of (R)-3-Boc-aminopiperidine and relates to the technical field of preparation of piperidine heterocyclic compounds. The preparation method includes following steps: (1) with N-Cbz-3-piperidinecarboxylic acid as a raw material, performing chiral resolution with R-phenylethylamine to obtain a compound I; (2) performing an acid-amide condensation reaction to the compound I and ammonia gas to obtain a compound II; (3) performing a Hofmann degradation reaction to the compound II to obtain a compound III; (4) performing protection to the compound III with di-tert-butyl dicarbonate to obtain a compound IV; and (5) performing a hydrogenation and Cbz-removal reaction to the compound IV to prepare the (R)-3-Boc-aminopiperidine. The method is mild in reaction conditions, is safe and reliable, is excellent in process stability, is low in energy consumption, is high in yield, is green and environment-protective and is suitable for industrial production.
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Paragraph 0064; 0065; 0066; 0067; 0068; 0069; 0070
(2018/04/03)
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- Amino-protected (R) - 3-amino-piperidine preparation method
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The invention discloses a preparation method of amino protection (R)-3-amino piperidine, and the preparation method comprises the following steps: (1) in the presence of a first solvent or absence of a solvent, reacting a compound of formula V with benzylamine to obtain a compound of formula VI; (2) in the presence of a second solvent, performing catalytic hydrogenation of the compound of formula VI to remove benzyl to obtain the amino protection (R)-3-amino piperidine. According to the method, the defects of use of expensive metal catalysts and use of high-pressure hydrogenation and various splitting for synthesis of a chiral amino piperidine ring can be avoided, at the same time, the synthetic route is short, the process is simple, the yield is high, and the method is suitable for industrial mass production.
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- (R) - 3-amino-piperidine dihydrochloride preparation method
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The invention discloses a method for preparing (R)-3-amino piperidine hydrochloride. D-glutamic acid is taken as a starting material, and the (R)-3-amino piperidine hydrochloride is obtained by reaction in the following five steps: (1) hydroxyl esterification and amido Boc protection; (2) ester reduction; (3) hydroxyl activation; (4) cyclization; (5) amino Boc removal protection. The preparation method disclosed by the invention is short in synthetic route and low in cost, and industrial production can be achieved.
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Paragraph 0029; 0040-0042
(2017/01/09)
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- Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors
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High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50values of 0.024?nM and 0.095?nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50?=?28?nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication.
- Wurz, Ryan P.,Sastri, Christine,D'Amico, Derin C.,Herberich, Brad,Jackson, Claire L.M.,Pettus, Liping H.,Tasker, Andrew S.,Wu, Bin,Guerrero, Nadia,Lipford, J. Russell,Winston, Jeffrey T.,Yang, Yajing,Wang, Paul,Nguyen, Yen,Andrews, Kristin L.,Huang, Xin,Lee, Matthew R.,Mohr, Christopher,Zhang,Reid, Darren L.,Xu, Yang,Zhou, Yihong,Wang, Hui-Ling
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p. 5580 - 5590
(2016/11/09)
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- MANUFACTURING METHOD FOR A PIPERIDINE-3-YLCARBAMATE COMPOUND AND OPTICAL RESOLUTION METHOD THEREFOR
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Provided is a manufacturing method for a piperidin-3-ylcarbamate compound in which a pyridin-3-ylcarbamate compound and hydrogen are brought into contact in the presence of a palladium catalyst.
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Page/Page column 19
(2011/01/12)
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- STEREOSELECTIVE SYNTHESIS OF PIPERIDINE DERIVATIVES
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This invention relates to dialdehyde or dinitrile compounds, which are useful for stereoselective synthesis of piperidine, pyrrolidine, and azepane derivatives.
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Page/Page column 15
(2010/06/22)
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- TETRAHYDRO-IMIDAZOY1,5-A¨PYRAZINE DERIVATIVES, PREPARATION METHODS AND MEDICAL USES THEREOF
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Tetrahydro-imidazo[1,5-a]pyrazine derivatives of formula ( I ), their preparation methods, pharmaceutical compositions containing the derivatives and uses thereof as medicaments, especially as dipeptidyl peptidase IV inhibitor, wherein the substituents of formula ( I ) are defined as same as the description.
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Page/Page column 30
(2010/10/03)
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- PREVENTIVE OR THERAPEUTIC AGENTS FOR MULTIPLE SCLEROSIS
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The preventive or therapeutic agents of the present invention for multiple sclerosis comprise compounds represented by the following formula (I), or salts or hydrates thereof, [wherein, T1, X, Z1, Z2, and R1 have the same meaning as T1, X, Z1, Z2, and R1 in this application].
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Page/Page column 47
(2010/11/28)
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- New substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
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The present invention relates to substituted imidazo-pyridinones and imidazo-pyridazinones of general formula wherein R1 to R4 are defined as in claim 1, the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
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Page/Page column 12
(2008/06/13)
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- COMBINATION DRUG
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The present invention provides pharmaceutical agents comprising a dipeptidyl peptidase IV (DPPIV) inhibitor and a biguanide agent in combination, which enhance the effects of active circulating glucagon-like peptide-1 (GLP-1) and/or active circulating glucagon-like peptide-2 (GLP-2).
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Page/Page column 84
(2010/02/12)
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- 1,3-DIHYDROIMIDAZOLE FUSED-RING COMPOUND
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The objective of this invention is to provide novel compounds that show excellent DPPIV-inhibiting activity. The present invention provides compounds represented by the general formula (I), salts thereof, or hydrates thereof, [wherein,T1 stands for a monocyclic or bicyclic 4 to 12-membered heterocycle having 1 or 2 nitrogen atoms in the ring, which may have substituents; in formula (I), the following formula represents a double bond or a single bond; X3 denotes an oxygen atom or a sulfur atom; X1 denotes a C2-6 alkynyl group which may have substituents; Z1 denotes a nitrogen atom or the formula -CR3=; Z2 and Z3 each independently denote a nitrogen atom, the formula -CR1=, a carbonyl group, or the formula -NR2-; R1, R2, R3, and X2 each independently denote a C1-6 alkyl group which may have substituents, and such].
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Page/Page column 41
(2008/06/13)
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- Antibacterial compounds
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Bacterial protein synthesis-inhibiting compounds having formula (I) and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates in the processes, compositions containing the compounds, and methods of using the compounds are disclosed.
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Page/Page column 18
(2010/02/12)
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- SUCCINATE SALTS OF HETEROCYCLIC DPP-IV INHIBITORS
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The present invention relates to therapeutically active and selective hemisuccinate salts of inhibitors of the enzyme DPP-IV of formula (I), pharmaceutical compositions comprising the salts and the use of such salts for and the manufacture of medicaments for treating diseases that are associated with proteins that are subject to inactivation by DPP-IV, such as type 2 diabetes and obesity.
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- Heterocyclic substituted aminoazacycles useful as central nervous system agents
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Heterocyclic substituted aminoazacyclic compounds of the formula (I):Z-R3, wherein Z is a defined aminoazacycle and R3 is a defined heterocycle moiety, pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.
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- PROCESS FOR PRODUCING 1-ALKOXYCARBONYL NITROGENOUS SATURATED HETEROCYCLIC DERIVATIVE
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A method for producing N-protected heterocyclic compounds such as 1-alkoxycarbonyl-3-aminopyrrolidines through position-selective reaction at the nitrogen atom that constitutes the hetero ring of a nitrogen-containing saturated heterocyclic compound having two nitrogen atoms such as 3-aminopyrrolidine. A dialkyl dicarbonate (ROCO-O-COOR) is reacted with a nitrogen-containing saturated heterocyclic compounds having two nitrogen atoms, at pH of from 9 to 14 to obtain a high-purity 1-alkoxycarbonyl nitrogen-containing saturated heterocyclic compound.
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- Condensed imidazole derivatives
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The present invention is related to compounds represented by the following formula, or salts or hydrates thereof wherein, T1 represents a 4- to 12-membered heterocyclic group containing one or two nitrogen atoms in the ring, which is a monocyclic or bicyclic structure that may have one or more substituents; X represents a C1-6 alkyl group which may have one or more substituents, or such; Z1 and Z2 each independently represent a nitrogen atom or a group represented by the formula —CR2—; R1 and R2 independently represent a hydrogen atom, a C1-6 alkyl group which may have one or more substituents, or a C1-6 alkoxy group which may have one or more substituents, or such. These are novel compounds that exhibit an excellent DPPIV-inhibiting activity.
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- HETEROCYCLIC COMPOUNDS THAT ARE INHIBITORS OF THE ENZYME DPP-IV
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The present invention relates to therapeutically active and selective inhibitors of the enzyme DPP-IV of formula I, pharmaceutical compositions comprising the compounds and the use of such compounds for and the manufacture of medicaments for treating diseases that are associated with proteins that are subject to inactivation by DPP-IV, such as type 2 diabetes and obesity.
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- An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines
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Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.
- Moon, Sung-Hwan,Lee, Sujin
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p. 3919 - 3926
(2007/10/03)
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