41288-96-4Relevant academic research and scientific papers
An alternative synthesis of 2-chloro-5-hydroxypyridine: A key component of the non-opioid analgesic agent ABT-594
Krow,Xiao,Cannon,Swan,Nickel
, p. 4093 - 4096 (2000)
The synthesis of the biologically useful synthon 2-chloro-5-hydroxypyridine from 3-iodo-6-chloropyridine is described.
A practical synthesis of an aminopyridine as a component of a BTK inhibitor
Alabanza, Lady Mae,Dong, Yan,Wang, Ping,Wright, James A.,Zhang, Yingchao,Briggs, Andrew J.
, p. 876 - 880 (2013)
Development of a new route to the BTK intermediate, 5-(1-(azetidin-1-yl)-2- methylpropan-2-yloxy)pyridin-2-amine (7), has resulted in significant improvements in terms of yield, purity, and operability over the previously known synthesis. The new route was demonstrated on a multihundred-gram scale, and the overall yield of 7 from 2-chloro-5-hydroxypyridine (1) was improved to 72%. Lithium aluminum hydride, a Swern oxidation, cesium carbonate, azetidine free base, and four chromatographic purifications used in the earlier synthesis were eliminated.
Identification of an Oxalamide Ligand for Copper-Catalyzed C?O Couplings from a Pharmaceutical Compound Library
Chan, Vincent S.,Krabbe, Scott W.,Li, Changfeng,Sun, Lijie,Liu, Yue,Nett, Alex J.
, (2019/04/30)
A typical pharmaceutical compound library is stocked with molecular diversity and could provide a platform for the discovery of new ligand structures. Herein, we describe the use of this approach in combination with high throughput screening to identify N,N’-bis(thiophene-2-ylmethyl)oxalamide as a ligand that is generally effective for copper-catalyzed C?O cross-couplings to prepare both biarylethers as well as phenols under mild conditions.
Photoredox Properties of Homoleptic d6 Metal Complexes with the Electron-Rich 4,4′,5,5′-Tetramethoxy-2,2′-bipyridine Ligand
Büldt, Laura A.,Prescimone, Alessandro,Neuburger, Markus,Wenger, Oliver S.
, p. 4666 - 4677 (2015/10/20)
A synthetic procedure leading to 4,4′,5,5′-tetramethoxy-2,2′-bipyridine [(MeO)4bpy] was developed, and the first three metal complexes with this ligand were synthesized. A few ligand precursor compounds, the final ligand, and its homoleptic iron(II) complex were characterized structurally by X-ray diffraction. The combination of cyclic voltammetry, optical absorption, luminescence, and transient absorption spectroscopy provided detailed insight into the electronic structure of the entire series of homoleptic FeII, RuII, and OsII complexes. The ruthenium(II) complex is a more potent photoreductant than the [Ru(bpy)3]2+ parent compound by approximately 0.4 V as confirmed by 3MLCT excited-state quenching experiments with a relatively mild oxidant, 1-chloro-4-nitrobenzene. In the presence of methanesulfonic acid in CH3CN, the photoexcited [Ru{(MeO)4bpy}3]2+ complex is able to undergo proton-coupled electron transfer (PCET) with acetophenone to yield a ketyl radical. Chemically robust and potent photoreductants are of interest for the phototriggering of electron-transfer reactions, for example, in photoredox catalysis, in dye-sensitized solar cells, in fundamental studies of (proton-coupled) electron transfer, or for the generation of solvated electrons.
Investigation of functionalized α-chloroalkyllithiums for a stereospecific reagent-controlled homologation approach to the analgesic alkaloid (-)-epibatidine
Emerson, Christopher R.,Zakharov, Lev N.,Blakemore, Paul R.
supporting information, p. 16342 - 16356 (2013/12/04)
Four putative functionalized α-chloroakyllithiums RCH 2CHLiCl, where R=CHCH2 (18 a), CCH (18 b), CH 2OBn (18 c), and CH[O(CH2)2O] (18 d), were generated in situ by sulfoxide-lithium exchange from α-chlorosulfoxides, and investigated for the stereospecific reagent-controlled homologation (StReCH) of phenethyl and 2-chloropyrid-5-yl (17) pinacol boronic esters. Deuterium labeling experiments revealed that α-chloroalkyllithiums are quenched by proton transfer from their α-chlorosulfoxide precursors and it was established that this effect compromises the yield of StReCH reactions. Use of α-deuterated α-chlorosulfoxides was discovered to ameliorate the problem by retarding the rate of acid-base chemistry between the carbenoid and its precursor. Carbenoids 18 a and 18 b showed poor StReCH efficacy, particularly the propargyl group bearing carbenoid 18 b, the instability of which was attributed to a facile 1,2-hydride shift. By contrast, 18 d, a carbenoid that benefits from a stabilizing interaction between O and Li atoms gave good StReCH yields. Boronate 17 was chain extended by carbenoids 18 a, 18 b, and 18 d in 16, 0, and 68 % yield, respectively; α-deuterated isotopomers D-18 a and D-18 d gave yields of 33 and 79 % for the same reaction. Double StReCH of 17 was pursued to target contiguous stereodiads appropriate for the total synthesis of (-)-epibatidine (15). One-pot double StReCH of boronate 17 by two exposures to (S)-D-18 a (≤66 % ee), followed by work-up with KOOH, gave the expected stereodiad product in 16 % yield (d.r.～67:33). The comparable reaction using two exposures to (S)-D-18 d (≤90 % ee) delivered the expected bisacetal containing stereodiad (R,R)-DD-48 in 40 % yield (≥98 % ee, d.r.=85:15). Double StReCH of 17 using (S)-D-18 d (≤90 % ee) followed by (R)-D-18 d (≤90 % ee) likewise gave (R,S)-DD-48 in 49 % yield (≥97 % ee, d.r.=79:21). (R,S)-DD-48 was converted to a dideuterated isotopomer of a synthetic intermediate in Corey's synthesis of 15. Copyright
Oxidation of organotrifluoroborates via oxone
Molander, Gary A.,Cavalcanti, Livia N.
experimental part, p. 623 - 630 (2011/03/20)
A method for the oxidation of organotrifluoroborates using Oxone was developed. A variety of aryl-, heteroaryl-, alkenyl-, and alkyltrifluoroborates were converted into the corresponding oxidized products in excellent yields. This method proved to be tolerant of a broad range of functional groups, and in secondary alkyl substrates it was demonstrated to be completely stereospecific.
AMIDOPYRAZOLE DERIVATIVE
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Page/Page column 24, (2010/11/23)
A platelet coagulation inhibitor which inhibits neither COX-1 nor COX-2 is provided. The inhibitor is a compound represented by general formula (I): wherein Ar1 and Ar2 independently represent a 5- or 6-membered aromatic heterocyclic group optionally substituted with 1 to 3 substituents, or a phenyl group optionally substituted with 1 to 3 substituents; R1 represents a lower acyl group, carboxyl group, a lower alkoxycarbonyl group, a lower alkoxy group, a lower alkyl group optionally substituted with 1 or 2 substituents, a carbamoyl group optionally substituted with 1 or 2 substituents, an oxamoyl group optionally substituted with 1 or 2 substituents, an amino group optionally substituted with 1 or 2 substituents, a 4- to 7-membered alicyclic heterocyclic group optionally substituted with 1 or 2 substituents, a phenyl group optionally substituted with 1 to 3 substituents, or a 5- or 6-membered aromatic heterocyclic group optionally substituted with 1 to 3 substituents; and R2 represents hydrogen atom, a halogeno group, or the like.
Efficient synthesis of halohydroxypyridines by hydroxydeboronation
Voisin, Anne Sophie,Bouillon, Alexandre,Lancelot, Jean-Charles,Rault, Sylvain
, p. 1417 - 1421 (2007/10/03)
This paper describes a general method for the synthesis of halohydroxypyridines from novel halopyridinylboronic acids and esters recently described by some of us. Halopyridinylboronic acids and esters have been efficiently hydroxydeboronated under mild conditions by employing hydrogen peroxide or meta-chloroperbenzoic acid. These hydroxylations take place regioselectively without other oxidation (N-oxide formation).
5-HT1F agonists
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Page column 20, (2008/06/13)
The present invention relates to substituted furo[3,2-b]pyridine compounds of formula I: or a pharmaceutical acid addition salt thereof; where; R is E—D is C═CH or CH—CH2; R1is hydrogen or C1-C4alkyl; R2is hydrogen, halo, hydroxy, —NR3R4, —SR3, —C(O)R3, —C(O)MR3R4, —NR3SO2R5, —NHC(Q)NR3R4, —NHC(O)OR3, or —NR3C(O)R5; R3, R4, and R5are independently hydrogen, C1-C4alkyl, C2-C6alkenyl, C2-C6alkynyl, or —(CH2)naryl; or R3and R4combine, together with the nitrogen to which they are attached, form a pyrrolidine, piperidine, piperazine, 4-substituted piperazine, morpholine, or thiomorpholine ring; n is 0, 1, 2, 3, 4, 5, or 6; and Q is O or S. The present invention further relates to pharmaceutical. formulations containing compounds formula I and to the use of compounds of formula I for activating 5-HT1Freceptors, inhibiting neuronal protein extravasation, and treating and/or preventing migraine in a mammal.
TRIAZOLO-PYRIDINES AS ANTI-INFLAMMATORY COMPOUNDS
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Page 85, (2010/02/08)
The present invention relates to novel triazolo-pyridines of the formula (I) wherein X is >CH2, >NH, sulfur, >S=O, >S02 or oxygen; wherein said >CH2 and >NH may optionally be substituted with a suitable substituent; R1 is selected from the group consisting of hydrogen, (C1-C6)alkyl and other suitable substituents; R2 is selected from the group consisting of hydrogen, (Cl-C6)alkyl and other suitable 10 substituents; s is an integer from 0-4; R3 is R4, R5-(NR6)-, R5-S-, R5-(S=O)-, R5-(S02)-, R5-S02-NR6-, R5-(NR6)-S02-, R5-O-,R5-(C=O)-, R5-(NR6)-(C=O)-, R5-(C=O)-NR6-, R5-O-(C=O)-, R5-(C=O)-O-, R5-CR7=CR8- or R5-C=-C-; such that the molecular weight of R3 is less than 500 AMU, preferably less than 250 15 AMU; R4, R5 and R6 are each selected from the group consisting of hydrogen, (C1-C6)alkyl and other suitable substituents; or a pharmaceutically acceptable salt thereof; to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the present invention are potent inhibitors of MAP kinases. They are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.
