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56553-60-7Relevant articles and documents
A β-enaminone-initiated multicomponent domino reaction for the synthesis of indoloquinolizines and benzoquinolizines from acyclic precursors
Suryavanshi, Padmakar A.,Sridharan, Vellaisamy,Menéndez, J. Carlos
, p. 13207 - 13215 (2013)
The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two C-C and two C-N bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet-Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4- dimethoxyphenylethylamine) prevents the Pictet-Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a] quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers. One operation, four bonds: The cerium(IV) ammonium nitrate (CAN)-catalyzed reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords indolo[2,3-a]quinolizines in a single operation (see scheme). This multicomponent reaction creates two rings by generating two C-C and two C-N bonds, and is proposed to take place through a domino process that involves at least five individual reactions. Copyright
Synthesis from (+)-α-pinene of optically active macrocycles containing cyclobutane, ester, azine, or hydrazide groups
Ishmuratov,Mingaleeva,Shakhanova,Muslukhov,Yakovleva,Botsman,Tolstikov
, p. 210 - 214 (2011)
Optically active symmetric macrocyclic diesterazines and diesterdihydrazides were synthesized efficiently from the available natural monoterpene (+)-α-pinene (de 50%) using a [2+1]-reaction of 1'-[(1S,3S)-3-(2-hydroxyethyl)-2,2-dimethylcyclobutyl]ethanone and glutaric and adipic acid chlorides followed by [1+1]-condensation of the intermediate diketodiesters with hydrazine hydrate or glutaric acid dihydrazide.
Application of thermal analytical techniques in development of a safe and robust process for production of triacetoxyborohydride (STAB)
Lam, Thientu T.,Bagner, Carl,Tuma, Linda
, p. 109 - 113 (2005)
The thermal hazards associated with the original procedure to produce sodium triacetoxyborohydride (STAB) from the reaction of NaBH4 with glacial acetic acid were identified using various thermal analytical techniques. A substantial amount of NaBH4 reagent accumulated at the end of the addition. As a result, a large heat spike occurred in the subsequent temperature ramp, which had the potential to initiate STAB decomposition and to generate a significant amount of non-condensable gases. Moreover, this rapid heat release was also accompanied by a rapid and uncontrollable generation of hydrogen gas from consumption of the accumulated NaBH4. Evaluation of the reaction kinetics provided the fundamental information needed to develop a safe and robust process. The current procedure, utilizing a solution of NaBH4 in DMAC, provides sufficient control of the heat and hydrogen gas release rates to reduce the processing hazard and eliminate the requirement for specially rated equipment for charging the NaBH4 solids to the reactor.
Two-step stereocontrolled synthesis of densely functionalized cyclic β-aminoesters containing four stereocenters, based on a new cerium(IV) ammonium nitrate catalyzed sequential three-component reaction
Sridharan, Vellaisamy,Menendez, J. Carlos
, p. 4303 - 4306 (2008)
(Chemical Equation Presented) The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential, one-pot reaction between alkylamines, β-ketoesters, and chalcones afforded cis-4,6-disubstituted 2-alkylaminocyclohexene-1-carboxylic esters with complete diastereoselectivity. The carbon-carbon double bond of these compounds was reduced with sodium triacetoxyborohydride, again with complete diastereoselectivity. This novel two-step route allows the transformation of very simple acyclic starting materials into tetrasubstituted cyclohexane derivatives bearing four functional groups, including a cis-β-aminoester moiety, and generates four stereocenters, three of which are adjacent and one of which is quaternary.
Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D
Mock, Elliot D.,Kotsogianni, Ioli,Driever, Wouter P. F.,Fonseca, Carmen S.,Vooijs, Jelle M.,Den Dulk, Hans,Van Boeckel, Constant A. A.,Van Der Stelt, Mario
, p. 481 - 515 (2021/02/05)
N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of N-acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported N-(cyclopropylmethyl)-6-((S)-3-hydroxypyrrolidin-1-yl)-2-((S)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (1, LEI-401) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [ Mock et al. Nat Chem. Biol., 2020, 16, 667-675 ]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of LEI-401. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an N-methylphenethylamine group by replacement with an (S)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (S)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording LEI-401 as a nanomolar potent inhibitor with drug-like properties. LEI-401 is a suitable pharmacological tool compound to investigate NAPE-PLD function in vitro and in vivo.
Total Synthesis of Ritterazine B
Nakayama, Yasuaki,Maser, Michael R.,Okita, Tatsuya,Dubrovskiy, Anton V.,Campbell, Taryn L.,Reisman, Sarah E.
supporting information, p. 4187 - 4192 (2021/04/06)
The first total synthesis of the cytotoxic alkaloid ritterazine B is reported. The synthesis features a unified approach to both steroid subunits, employing a titanium-mediated propargylation reaction to achieve divergence from a common precursor. Other key steps include gold-catalyzed cycloisomerizations that install both spiroketals and late stage C-H oxidation to incorporate the C7′ alcohol.
Synthesis of 1,4-Diazepanes and Benzo[ b][1,4]diazepines by a Domino Process Involving the in Situ Generation of an Aza-Nazarov Reagent
Maiti, Swarupananda,Leonardi, Marco,Cores, ángel,Tenti, Giammarco,Ramos, M. Teresa,Villacampa, Mercedes,Menéndez, J. Carlos
, p. 11924 - 11933 (2020/10/23)
A step-and atom-economical protocol allowing the synthesis of 1,4-diazepanes and also tetrahydro-and decahydro-1,5-benzodiazepines is described. The method proceeds from very simple starting materials such as 1,2-diamines and alkyl 3-oxohex-5-enoates and can be performed under solvent-free conditions in many instances. The key event of this process was the generation in situ of an aza-Nazarov reagent and its subsequent intramolecular aza-Michael cyclization. An intermolecular version of the reaction was also established and applied to the synthesis of the first example of the pyrrolo[1,2-A][1,5]diazonine framework.
Low-cost method preparation for doxazosin mesylate controlled release tablets
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Paragraph 0017; 0018, (2019/07/01)
The invention relates to a preparation method of doxazosin mesylate controlled release tablets for treating urination disorder caused by prostatic hyperplasia, and belongs to the field of medicines. The invention provides a low-cost preparation method for doxazosin mesylate controlled release tablets.
Expanding dynamic kinetic protocols: Transaminase-catalyzed synthesis of α-substituted β-amino ester derivatives
Cuetos, Anibal,Lavandera, Ivan,Gotor, Vicente
supporting information, p. 10688 - 10690 (2013/11/06)
Several α-alkylated β-amino esters have been obtained via DKR processes employing a kit of transaminases and isopropylamine as an amino donor in aqueous medium under mild conditions. Thus, while acyclic α-alkyl-β-keto esters afforded excellent conversions and enantioselectivities, although usually low diastereoselectivities, using more constrained cyclic β-keto esters high to excellent inductions were obtained.
PROCESSES FOR PREPARING CINACALCET HYDROCHLORIDE AND POLYMORPHIC FORMS THEREOF
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Page/Page column 19, (2008/12/06)
The invention relates to cinacalcet hydrochloride, new polymorphic crystalline forms of cinacalcet hydrochloride, amorphous cinacalcet hydrochloride and synthetic processes for their preparation.
