Concise Synthesis of Key Intermediates of Pyriftalid and Paquinimod via Hydrogenation Method

Published on Aug 21, 2017in Organic Process Research & Development3.023
· DOI :10.1021/ACS.OPRD.7B00177
Zhong Li1
Estimated H-index: 1
,
Bing Li1
Estimated H-index: 1
+ 1 AuthorsFu-Li Zhang2
Estimated H-index: 2
Sources
Abstract
An efficient and scalable synthesis of 7-amino-3-methylisobenzofuran-1(3H)-one (1) and 2-amino-6-ethylbenzoic acid (2) has been developed via a one-step catalytic hydrogenation. The triethylammonium salt of 2-acetyl-6-nitrobenzoic acid was used as the starting material and 1 was prepared in a biphasic solvent system of toluene/H2O, while 2 was obtained when the solvent was replaced with H2O. Intermediates 1 and 2 could be used to synthesize Pyriftalid and Paquinimod, respectively.
📖 Papers frequently viewed together
16 Citations
14 Citations
6 Citations
References9
Newest
#1Andreas Faust (WWU: University of Münster)H-Index: 20
#2Tom VöllerH-Index: 4
Last. Thomas Vogl (WWU: University of Münster)H-Index: 61
view all 7 authors...
The establishment of novel molecular imaging tools to monitor the local activity of inflammation remains an interdisciplinary challenge. Our target, the alarmin S100A9, one subunit of the heterodimer S100A8/S100A9 (calprotectin), is locally secreted in high concentrations from immigrated and activated phagocytes at local sites of inflammation. Calprotectin is already a well established serum biomarker for many inflammatory disorders. Here we show the development and first evaluation of the novel...
15 CitationsSource
#1Anastasia Markopoulou (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 2
#2Vasileios C. Kyttaris (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 38
Abstract Advances in the understanding of the cellular biological events that underlie systemic lupus erythematosus (SLE) have led to the identification of key molecules and signaling pathways that are aberrantly expressed. The parallel development of small molecule drugs that inhibit or interfere with the specific perturbations identified, offers perspective for more rational, effective and less toxic therapy. In this review, we present data from preclinical and clinical studies of such emergin...
25 CitationsSource
#1Hans-Ulrich BlaserH-Index: 45
#2Heinz SteinerH-Index: 9
Last. Martin Studer (Hoffmann-La Roche)H-Index: 23
view all 3 authors...
In this update, progress made in the last decade for the selective catalytic hydrogenation of nitroarenes in the presence of other reducible functions is reviewed. The main focus is on catalytic systems capable of reducing nitro groups with very high chemoselectivity in substrates containing carbon–carbon or carbon–nitrogen double or triple bonds, carbonyl or benzyl groups, and multiple Cl, Br, or I substituents. The performance of new catalyst types is described, most notably of gold-based cata...
475 CitationsSource
#1Stig JönssonH-Index: 7
#2Gunnar AnderssonH-Index: 91
Last. Anders BjörkH-Index: 2
view all 13 authors...
Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure−activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the ...
154 CitationsSource
#1Kazuyuki Hattori (Gifu Pharmaceutical University)H-Index: 16
#2Hironao Sajiki (Gifu Pharmaceutical University)H-Index: 60
Last. Kosaku Hirota (Gifu Pharmaceutical University)H-Index: 39
view all 3 authors...
Abstract The hydrogenolysis of aromatic ketones and aldehydes quite smoothly give the corresponding methylene compounds via the formation of the intermediary benzyl alcohols in the presence of Pd/C as a catalyst. Therefore, it is extremely difficult to isolate the intermediary benzyl alcohol selectively. This paper describes a mild and chemoselective hydrogenation method of an aromatic carbonyl compound to benzyl alcohol using the 10% Pd/C(en) catalyst and its application to the chemoselective d...
98 CitationsSource
#1Christoph Lüthy (Syngenta)H-Index: 1
#2Zondler Helmut (Syngenta)H-Index: 1
Last. James Allen (Syngenta)H-Index: 1
view all 8 authors...
A series of novel types of 7-(4,6-dimethoxypyrimidin-2-yl)oxy - and -thio-3-methyl-1 (3H)-isobenzofuranones were discovered at Dr R Maag AG. From the thio-isobenzofuranyl series, CGA 279 233—BSI-proposed common name pyriftalid—was chosen for further development as a grass herbicide for use in rice. General synthetic approaches to these new phthalic acid-derived compounds are given, with emphasis on the synthesis of pyriftalid and its physico-chemical behaviour. © 2001 Society of Chemical Industr...
21 CitationsSource
#1Jörg Durner (University of Konstanz)H-Index: 9
#2Valérie GailusH-Index: 4
Last. Peter BögerH-Index: 55
view all 3 authors...
Abstract In addition to the synthesis of ketolacids the enzyme acetolactate synthase shows an oxygen-consuming side reaction. Partially purified acctolactate synthase from corn (Zea mays L.) and barley (Hordeum vulgare L.) exhibits chemiluminescence in the presence of oxygen, Mn2+ and low concentrations of pyruvate. Light emission is inhibited by azide, but not by catalase or superoxide dismutase. The data suggest the formation of singlet oxygen during the catalytic cycle, and provides a basis f...
13 CitationsSource
In addition to the physiological reactions catalyzed by acetolactate synthase, it supports an oxygen-consuming side reaction. Although the synthase and oxygenase activities are activated to somewhat different extents by various metals (Mn2+, Mg2+, Ca2+, Coz+, Zn2+, Ni2+, Cd2+, Cu2+, Ba2+, A13+), the modest degree of these differences (at most 6-fold) and the high degree of promiscuity of the enzyme with respect to its metal requirement suggest that the metal is not intimately involved in the che...
37 CitationsSource
18 CitationsSource
Cited By1
Newest
#1Dragan Zlatković (University of Graz)
#2Doris Dallinger (University of Graz)H-Index: 25
Last. C. Oliver Kappe (University of Graz)H-Index: 94
view all 3 authors...
Flash vacuum pyrolysis of methyl N-methyl-N-nitrosoanthranilate leads to elimination of nitric oxide and disproportionation of the formed N-radical to 7-(methylamino)phthalide and methyl N-methylanthranilate. This transformation was found to be a convenient, solvent-free method for the preparation of 7-(methylamino)phthalides. An alternative route through pyrolysis of N-benzyl-N-methyl anthranilates was also investigated.
Source