- Simple synthetic process of 6-methoxypyridine-3-formaldehyde
-
The invention relates to a synthesis process of 6-methoxypyridine-3-formaldehyde, which comprises the following steps: 1, reacting 6-bromo-3-methylpyridine with sodium methylate under the condition ofa dry protic solvent to obtain 6-methoxy-3-methylpyridine; 2, carrying out bromination reaction on the 6-methoxy-3-methylpyridine obtained in the step 1 with a bromination reagent in an aprotic solvent under the action of a catalyst to obtain 5-(dibromomethyl)-2-methoxypyridine; and 3, carrying out a hydrolysis reaction on the 5-(dibromomethyl)-2-methoxypyridine prepared in the step 2 with an alkali in a mixed solvent of an aprotic solvent and water to prepare 6-methoxypyridine-3-formaldehyde. According to the invention, 6-bromo-3-methylpyridine is used as a main raw material, and is subjected to sodium methylate substitution, bromination and alkali metal hydroxide hydrolysis, such that a target compound is obtained. The method has the advantages of simple and accessible raw materials ineach step, simple process operation and mild reaction conditions, and is suitable for industrial amplification.
- -
-
Paragraph 0033; 0046-0049; 0051; 0058-0061
(2020/03/25)
-
- Visible-Light-Promoted Nickel- and Organic-Dye-Cocatalyzed Formylation Reaction of Aryl Halides and Triflates and Vinyl Bromides with Diethoxyacetic Acid as a Formyl Equivalent
-
A simple formylation reaction of aryl halides, aryl triflates, and vinyl bromides under synergistic nickel- and organic-dye-mediated photoredox catalysis is reported. Distinct from widely used palladium-catalyzed formylation processes, this reaction proceeds by a two-step mechanistic sequence involving initial in situ generation of the diethoxymethyl radical from diethoxyacetic acid by a 4CzIPN-mediated photoredox reaction. The formyl-radical equivalent then undergoes nickel-catalyzed substitution reactions with aryl halides and triflates and vinyl bromides to form the corresponding aldehyde products. Significantly, besides aryl bromides, less reactive aryl chlorides and triflates and vinyl halides serve as effective substrates for this process. Since the mild conditions involved in this reaction tolerate a plethora of functional groups, the process can be applied to the efficient preparation of diverse aromatic aldehydes.
- Huang, He,Li, Xiangmin,Yu, Chenguang,Zhang, Yueteng,Mariano, Patrick S.,Wang, Wei
-
supporting information
p. 1500 - 1505
(2017/02/05)
-
- Reversible Folding of a β-Hairpin Peptide by a Metal-Chelating Amino Acid
-
5-(1-Hydroxy-pyridin-2(1H)-onyl)-l-alanine (Hop) is a N-hydroxy-1,2-pyridone functionalized α-amino acid with the desired metal-chelating properties of DOPA (3,4-dihydroxy phenylalanine) but without its unwanted redox activity. The Fmoc-protected amino acid Fmoc-l-Hop(tBu)-OH (11) was synthesized from glycine phosphonate followed by enzymatic hydrolysis of the methyl ester yielding the Hop l-isomer in 96 % ee. The amino acid 11 is used in automated peptide synthesis for the assembly of a 14mer β-hairpin peptide with the sequence [dsb1, 14]H-CHXETGKHGHKLVC-OH (X=W, l-Hop). While the 10 π electron containing indole side chain of l-Trp in peptide 14 completes the formation of a hydrophobic cluster and results in 90 % folding, the folded fraction is significantly decreased to approximately 30 % for the 6 π electron l-Hop side chain in peptide 16. Metal chelation of Ga3+ reconstitutes the folding of 16 to above 60 % due to the formation of the Ga(16)3 trimer. The chelation process of 16 is monitored by NMR spectroscopy and the subsequent release of Ga3+ by a competitive metal chelator exemplifies the reversible oligomerization of peptide epitopes by metal chelation, bearing the opportunity to synthesize protein-sized aggregates on the basis of reversible chemistry in water.
- Reutzel, Jan,Diogo, Timm M.,Geyer, Armin
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p. 8450 - 8456
(2017/06/28)
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- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
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Page/Page column 741
(2016/04/10)
-
- NOVEL TETRAHYDROPYRIDOPYRIMIDINES AND TETRAHYDROPYRIDOPYRIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
-
The invention provides novel compounds having the general formula (I): wherein R1, R2, R3, Q, U,W, Z, X and Y are as described herein, compositions including the compounds and methods of using the compounds. These compounds are HbsAg inhibitors and are useful as medicaments for the treatment or prophylaxis of HBV infection.
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Page/Page column 157
(2016/07/27)
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- HETEROARYL SUBSTITUTED HETEROCYCLYL SULFONES
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The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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-
- Lewis basicity modulation of N-heterocycles: A key for successful cross-metathesis
-
Cross-metathesis involving N-heteroaromatic olefinic derivatives is disclosed. The introduction of an appropriate substituent on the heteroaromatic ring decreases the Lewis basicity of the nitrogen atom, thus preventing the deactivation of the ruthenium-centered catalyst. The reaction is quite general in terms of both N-heterocycles and olefinic partners.
- Lafaye, Kevin,Nicolas, Lionel,Gurinot, Amandine,Reymond, Sbastien,Cossy, Janine
-
supporting information
p. 4972 - 4975
(2015/01/08)
-
- Noncryogenic synthesis of functionalized 2-methoxypyridines by halogen-magnesium exchange using lithium dibutyl(isopropyl)magnesate(1-) and lithium chloride
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2-Methoxypyridines functionalized in the 3-, 5-, or 6-position and 2,6-dimethoxypyridines functionalized in the 3-position were prepared from the corresponding bromo or iodo analogues by using lithium dibutyl(isopropyl) magnesate(1-) and lithium chloride
- Struk, Lukasz,Sosnicki, Jacek G.
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p. 735 - 746
(2012/04/04)
-
- TRPA1 ANTAGONISTS
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Compounds of formula (I), wherein R1, R2, R3, and Y are defined in the description are TRPA1 antagonists. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 30
(2009/09/04)
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- Efficient synthesis of 5-functionalised 2-methoxypyridines and their transformation to bicyclic d-lactams, both accessed using magnesium ?ate? complexes as key reagents
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Simple and efficient synthesis of 5-functionalised ?2-methoxypyridines from 5-bromo-2-methoxypyridine using ?[n-Bu3Mg]Li performed in noncryogenic conditions is described. Application of 5-functionalised 2-methoxypyridines in the synthesis of 1-substitute
- So?nicki, Jacek G.
-
experimental part
p. 2508 - 2512
(2010/02/16)
-
- TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE
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Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.
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Page/Page column 90
(2010/11/28)
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- FIVE-MEMBERED HETEROCYCLIC DERIVATIVE
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The present invention relates to a compound represented by formula (I): a salt of the compound, or a solvate of the compound or the salt; a drug containing any of the compounds, the salts, and the solvates; a preventive and/or therapeutic agent for an ischemic disease containing any of the compounds, the salts, and the solvates; and a platelet coagulation inhibitor containing any of the compounds, the salts, and the solvates. The compound of the present invention is useful as a strong platelet coagulation inhibitor without inhibiting COX-1 or COX-2.
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Page/Page column 35
(2010/11/08)
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- Gonadotropin releasing hormone receptor antagonists
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The present invention relates to Gonadotropin Releasing Hormone (“GnRH”) (also known as Leutinizing Hormone Releasing Hormone) receptor antagonists.
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Page/Page column 27
(2010/02/15)
-
- Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis.
-
3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.
- Coleman, Paul J,Brashear, Karen M,Askew, Ben C,Hutchinson, John H,McVean, Carol A,Duong,Feuston, Bradley P,Fernandez-Metzler, Carmen,Gentile, Michael A,Hartman, George D,Kimmel, Donald B,Leu, Chih-Tai,Lipfert, Lorraine,Merkle, Kara,Pennypacker, Brenda,Prueksaritanont, Thomayant,Rodan, Gideon A,Wesolowski, Gregg A,Rodan, Sevgi B,Duggan, Mark E
-
p. 4829 - 4837
(2007/10/03)
-
- N-substituted heterocycles for the treatment of hypercholesteremia, dyslipidemia and other metabolic disorders; cancer, and other diseases
-
The present invention relates to certain compounds of Formula (I) which can be useful in the treatment of diseases, such as, cancer, metabolic disorders, Type 2 Diabetes, dyslipidemia and/or hyperchloesterolemia:
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-
- Oxime derivatives for the treatment of dyslipidemia and hypercholesteremia
-
The present invention relates to compounds of Formula (I) which may be useful in the treatment of diseases, such as, metabolic disorders, dyslipidemia and/or hyperchloesterolemia: 1
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-
- Heterocyclic derivatives for the treatment of diabetes and other diseases
-
The present invention relates to certain substituted heterocycles of Formula (I) which are useful in the treatment of diseases related to lipid and carbohydrate metabolism, such as type 2 diabetes, adipocyte differentiation, uncontrolled proliferation, such as lymphoma, Hodgkin's Disease, leukemia, breast cancer, prostate cancer or cancers in general; and inflammation, such as osteoarthritis, rheumatoid arthritis, Crohn's Disease or Inflammatory Bowel Disease.
- -
-
-
- Novel Compounds
-
The invention relates to heteroaromatic carboxamides of formula (I), wherein A, R1, R2 and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
-
- Piperidine derivatives
-
This invention relates to piperidine derivatives having antitumor activity and useful as pharmaceuticals such as an antitumor agent.
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-
-
- Therapeutic phenoxyalkylheterocycles
-
Compounds of the formula STR1 wherein Q is chosen from the group consisting of pyridyl, pyrazyl, pyrimidyl, quinolyl, indolyl and 7-azaindolyl or any of these substituted with one or two substituents; Y is an alkylene bridge of 3-9 carbon atoms; R1 and R2 are each independently chosen from hydrogen, halo, alkyl, alkenyl, amino, alkylthio, hydroxy, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, nitro, carboxy, alkoxycarbonyl, dialkylaminoalkyl, alkylaminoalkyl, aminoalkyl, difluoromethyl, trifluoromethyl or cyano; R3 is alkoxycarbonyl, alkyltetrazolyl, substituted or unsubstituted phenyl or heterocyclyl, the N-oxide thereof, or a pharmaceutically acceptable acid addition salt thereof is an effective antipicornaviral agent.
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-
- Electrochemical versus anionic oxygenation of azathymine derivatives
-
Pymetrozine (1) was converted to hemiaminal 2 in low to moderate yield by trapping its dianion with oxygen followed by reduction with ferrous salts. Pymetrozines 18 and 19 failed to undergo this type of oxygenation. All three pymetrozines were oxidized electrochemically at C5 to methyl hemiaminals 20, 21, and 22, respectively. Hydrolysis of 20 to 2 was accomplished under either acid- or base-catalyzed conditions in excellent yields, whereas the hydrolysis of methyl hemiaminals 21 and 22 was best performed under basic conditions. Soil metabolites of pymetrozine 1, hemiaminals 2 and 3, were prepared on a medium scale and in excellent yields. Linear sweep voltammetry data and conditions for preparative-scale electrochemistry are furnished for the precursory pymetrozines. Complete experimental and spectral data are provided for all new compounds, and the relative merits of anionic versus electrochemical oxidations for alkyl amides are discussed. A cautionary note is provided with the description of the conditions for large-scale anionic oxygenation because of potential explosive hazards.
- Butora, Gabor,Reed, Josephine W.,Hudlicky, Tomas,Brammer Jr., Larry E.,Higgs, Paul I.,Simmons, Dana P.,Heard, Nina E.
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p. 7694 - 7701
(2007/10/03)
-
- Substituted dipyridylethenes and -ethynes and key pyridine building blocks
-
Various new 2,5-disubstituted pyridines were prepared. The 2-substituted 5-formylpyridines 8, 15a-b were obtained by reduction of the nicotinic acid 3, hydrolysis of the bis(morpholino)methylpyridine 6 or the reaction of 5-bromopyridines 12 and 14 with lithium butoxide in DMF. Dipyridylethenes 16a-b,e were synthesized by Wadsworth-Emmons reaction with pyridyl phosphonate 7 or by coupling of the aldehydes by McMurry reaction to the ethenes 16c-d. After bromination of the C = C double bond of the dipyridylethenes 16a-d, dipyridylacetylenes 18a-d were obtained via elimination of the 1,2-dipyridyl-1,2-dibromoethanes 17a-d.
- Windscheif,Vogtle
-
-
- Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK and F 93574) and related compounds
-
The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described.Side-chains associated with H2 antagonist activity are attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring.Good H2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H2-receptor.High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models ledto compound 16c, 2--5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK and F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.H2-receptor antagonists / 2-amino-4-pyrimidones (isocytosines / imidazoles / thiazoles / pyridines / furans / 2-guanidinothiazoles / donetidine (SK and F 93574)
- Brown, T. H.,Blakemore, R. C.,Durant, G. J.,Ganellin, C. R.,Parsons, M. E.,et al.
-
p. 601 - 608
(2007/10/02)
-
- New amino acids from the poisonous mushroom Clitocybe acromelalga
-
New amino acids, L-3-(2-carboxy-4-pyrrolyl)-alanine (1) and L-3-(2-oxo-5-pyridyl)-alanine (2), were isolated from Clitocybe acromelalga and their structures were deduced by spectral data and biogenesis and confirmed by syntheses. Stizolobic acid (5) was also found in this fungus.
- Yamano, Kimiaki,Shirahama, Haruhisa
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p. 1457 - 1464
(2007/10/02)
-
- Process for the preparation of 2-chloro-5-chloromethylpyridine
-
A process for the preparation of 2-chloro-5-chloromethylpyridine of the formula (I) STR1 which is used as an intermediate for the preparation of insecticides, the process comprising (a) reacting in a first step nicotinic acid of the formula (II) STR2 with phosphorus pentachloride, if appropriate in the presence of thionyl chloride and if appropriate in the presence of a diluent, (b) reacting in a second step the resulting 3-trichloromethylpyridine from the first step, of the formula III, STR3 with an alkali metal alkoxide of the formual (IV) in which R represents alkyl and M represents an alkali metal cation, if appropriate in the presence of a diluent, (c) reacting in a third step the resulting pyridine ether acetal from the second step, of the formula (V), STR4 in which R has the abovementioned meaning with water, if appropriate in the presence of a catalyst acid, (d) hydrogenating in a fourth step the resulting pyridine aldehyde from the third step, of the formula (VI), STR5 in which R has the abovementioned meaning with molecular hydrogen in the presence of a hydrogenation catalyst and, if appropriate, in the presence of a diluent, and, finally, (e) reacting in a fifth step the resulting pyridylmethanol from the fourth step of the formula (VII), STR6 in which R has the abovementioned meaning.
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-
-
- Lithiation of Methoxypyridines Directed by α-Amino Alkoxides
-
The addition of methoxypyridinecarboxaldehydes to certain lithium dialkylamides gave α-amino alkoxides in situ that were ring-lithiated with alkyllithium bases.Alkylation and hydrolysis on workup provided ring-substituted methoxypyridinecarboxaldehydes via a one-pot reaction.The one-pot methylation of isomeric methoxypyridinecarboxaldehydes was examined.The regioselectivity of the lithiation-methylation was dependent on the aldehyde, the amine component of the α-amino alkoxide, and the metalation conditions.When lithiated N,N,N'-trimethylethylenediamine was used as the amine component of the α-amino alkoxide, methylation generally occured ortho to the aldehyde function.The analogous reactions using lithium N-methylpiperazide as the amine component gave substitution next to the methoxy group.Several new methylated methoxypyridinecarboxaldehydes were prepared in a regioselective manner by using this one-pot procedure.
- Comins, Daniel L.,Killpack, Michael O.
-
-
- Transformations of trichloromethyl groups during reactions of 3-trichloromethylpyridines with methoxide
-
When methoxide ion attacks an unsubstituted 2- or 6-position of a 3-trichloromethylpyridine, a hydrogen shift leads to a methoxy-substituted 3-dichloromethylpyridine. Further reaction of the dichloromethyl group with methoxide gives the corresponding acetal. This type of reaction has been applied to several chlorinated 3-trichloromethylpyridines and to 3- trichloromethylpyridine itself; a convenient synthesis of the latter is described.
- Dainter, Ronald S.,Jackson, Tracey,Omar, Abdirahman H. H.,Suschitzky, Hans,Wakefield, Basil J.,Hughes, Nigel,Nelson, Anthony J.,Varvounis, George
-
p. 283 - 287
(2007/10/02)
-
- 5-(HYDROXYPYRIDYLALKYL)-4-PYRIMIDONES
-
The compounds are substituted 2-amino-4-pyrimidones with a 5-(hydroxypyridylalkyl) substituent which are histamine H 2-antagonists. Two specific compounds are 2-2-(3-bromo-2-pyridylmethylthio) ethylamino!-5-(2-hydroxy-4-pyridylmethyl)-4-pyrimidone and 2-4-(3-methoxy-2-pyridyl)butylamino!-5-(2-hydroxy-4-pyridylmethyl)-4-pyrimido ne.
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-
- Pyrimidine compounds
-
The compounds are substituted pyrimidine compounds which are histamine H2 -antagonists. A specific compound of the present invention is 2-[2-(5-dimethylaminomethyl)-2-furylmethylthio)ethylamino]-5-(3-pyridylmethyl)-4-pyrimidone.
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