- One-pot synthesis of pyrrolidones from levulinic acid and amines/nitroarenes/nitriles over the Ir-PVP catalyst
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The synthesis of pyrrolidones via reductive amination of levulinic acid with aniline was examined over polypyrrolidone-stabilized metal nanoparticle catalysts. Among them, Ir metal was the most effective and applicable for the reductive amination of levulinic acid with nitroarenes/nitriles. Importantly, this catalyst was used for the one-pot synthesis of the anti-inflammatory drug indoprofen from 2-formylbenzoic acid and 2-(4-nitrophenyl)propanoic acid.
- Chaudhari, Chandan,Nagaoka, Katsutoshi,Nishida, Yoshihide,Sato, Katsutoshi,Shiraishi, Masaya
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supporting information
p. 7760 - 7764
(2020/11/27)
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- α-Angelica Lactone in a New Role: Facile Access to N-Aryl Tetrahydroisoquinolinones and Isoindolinones via Organocatalytic α-CH2 Oxygenation
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A method for the direct oxidation of various N-aryl tetrahydroisoquinolines and isoindolines to the corresponding lactams using α-angelica lactone as a catalyst was developed. The utility of the method was further demonstrated by synthesis of indoprofen and indobufen.
- Thatikonda, Thanusha,Deepake, Siddharth K.,Das, Utpal
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p. 2532 - 2535
(2019/04/16)
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- A g-C3N4-based heterogeneous photocatalyst for visible light mediated aerobic benzylic C-H oxygenations
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A metal-free heterogeneous photocatalytic system has been developed for highly efficient benzylic C-H oxygenations using oxygen as an oxidant. This visible light mediated oxidation reaction utilizes graphitic carbon nitride (g-C3N4) as a recyclable, nontoxic and low cost photocatalyst. Mild reaction conditions allow for the generation of synthetically and biologically valued isochromannones, phthalides, isoquinolinones, isoindolinones and xanthones from readily accessible alkyl aromatic precursors in good yields. The heterogeneous nature of the g-C3N4 catalytic system enables easy recovery and recycling as well as the use in multiple runs without loss of activity. The synthetic utility of this "green" methodology was further demonstrated by applying in bioactive and drug valued target syntheses.
- Geng, Pengxin,Tang, Yurong,Pan, Guanglong,Wang, Wentao,Hu, Jinchuan,Cai, Yunfei
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p. 6116 - 6122
(2019/11/20)
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- Application of the mild-condition phthalimidine synthesis with use of 1,2,3-1h-benzotriazole and 2-mercaptoethanol as dual synthetic auxiliaries. Effective synthesis of phthalimidines possessing a variety of substituents at 2-position
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The mild-condition phthalimidine synthesis based on Mannich type 1:1 condensation reaction between o-phthalaldehyde with a variety of primary amines in the presence of excess 2-mercaptoethanol and 1,2,3-1H-benzotriazole as "dual synthetic auxiliaries" in MeCN for 13 h at room temperature afford 2-substituted phthalimidines (2,3-dihydroisoindol-1-one) in fair to good isolated yields.
- Takahashi, Ichiro,Kawakami, Teruki,Hirano, Etsushi,Kimino, Mako,Kamimura, Shigeki,Miwa, Takayuki,Tamura, Takanori,Tazaki, Ryo,Kitajima, Hidehiko,Hatanaka, Minoru,Isa, Kimio,Hosoi, Shinzo
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p. 557 - 571
(2017/04/10)
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- Transition metal free intramolecular selective oxidative C(sp3)-N coupling: Synthesis of N-aryl-isoindolinones from 2-alkylbenzamides
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A synthetic method has been developed for the preparation of biologically important isoindolinones including indoprofen and DWP205190 drugs from 2-alkylbenzamide substrates by transition metal-free intramolecular selective oxidative coupling of C(sp3)-H and N-H bonds utilizing iodine, potassium carbonate and di-tert-butyl peroxide in acetonitrile at 110-140 °C.
- Verma, Ajay,Patel, Saket,Meenakshi,Kumar, Amit,Yadav, Abhimanyu,Kumar, Shailesh,Jana, Sadhan,Sharma, Shubham,Prasad, Ch. Durga,Kumar, Sangit
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p. 1371 - 1374
(2015/02/18)
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- Lactam coupling as a versatile route to indoprofen analogs
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A convergent synthesis of indoprofen via a Buchwald coupling approach is reported. Using this methodology, indoprofen and a set of analogs of indoprofen were readily prepared. Copyright
- Barnes, Keith D.,Chen, Ping,Chang, Yingyan,Lewis, Robert M.,Manley, Christopher M.,Mayhew, Nicholas J.,Steffke, Stephen H.,Wang, Guixing,Wang, Yi,Yang, Yuh-Lin A.,Lippert, John W.
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body text
p. 67 - 72
(2011/03/19)
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- Electrosynthesis of 2-arylpropionic acids from α-methylbenzyl chlorides and carbon dioxide by [Co(Salen)]
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The electrochemical synthesis of the 2-arylpropionic acid group of nonsteroidal anti-inflammatory agents such as ibuprofen, naproxen, indoprofen, biprofen, cicloprofen, and fenoprofen has been carried out in dimethylformamide (DMF) containing tetra-n-butylammonium perchlorate (nBu4NClO 4) by electrochemical carboxylation of α-methylbenzyl chlorides catalyzed by a schiff-base complex [Co(salen)] in an undivided cell equipped with a platinum cathode and magnesium anode under constant current density of 10 mA/cm2 in good yields. Cyclic voltammetric studies have also been carried out to investigate the mechanism by which [Co(salen)] catalyzes the cathodic reaction of α-methylbenzyl chlorides in presence of CO 2 by taking α-phenylethylchloride as the model compound. Copyright Taylor & Francis, Inc.
- Damodar,Krishna Mohan,Khaja Lateef,Jayarama Reddy
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p. 1143 - 1150
(2007/10/03)
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- A three-component coupling process based on vicarious nucleophilic substitution (VNSAR)-alkylation reactions: An approach to indoprofen and derivatives
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The intermediate anion derived from the vicarious nucleophilic substitution (VNS) of hydrogen reacts with a series of alkyl halides to generate the corresponding α-alkylated conventional VNS product in a one-pot process. This one-pot VNS-alkylation reaction offers a convenient route to a range α-substituted nitrobenzyl phosphine oxides, sulfones, and esters via a three-component coupling reaction. Reactions of α-chloroethyl phenyl sulfone (14) and ethyl 2-chloropropionate (16) with nitrobenzene followed by subsequent addition of an alkylating agent give a series of sulfones and esters bearing an α-aryl quaternary center. The VNS-alkylation protocol has been applied to the synthesis of derivatives of Indoprofen from nitrobenzene using readily available inexpensive starting materials. Indoprofen itself was prepared using the conventional VNS reaction in four steps and 24% overall yield from nitrobenzene.
- Lawrence, Nicholas J.,Liddle, John,Bushell, Simon M.,Jackson, David A.
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p. 457 - 464
(2007/10/03)
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- A facile preparation of phthalimides and a new approach to the synthesis of indoprofen via carbonylation
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This report describes an improved synthesis of a heterocyclic propionic acid, 2-4(1-oxo-2-isoindolinyl) phenyl propionic acid, Indoprofen (I) via carbonylation, a potent anti-inflammatory agent1 and an analgesic. The synthesis highlights the preparation of Indoprofen starting from readily available o-toluic acid and p-amino acetophenone by a sequence of reactions that included oxidative addition of carbonylation.
- Prasad, Chalasani S.N.,Varala, Ravi,Adapa, Srinivas R.
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p. 281 - 286
(2007/10/03)
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- Application of the phthalimidine synthesis with use of 1,2,3-1 H-benzotriazole and 2-mercaptoethanol as dual synthetic auxiliaries. Part 1. A simple synthesis of (±)-Indoprofen
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A representative nonsteroidal anti-inflammatory drug indoprofen is prepared in 4 steps from the commercially available 2-(4-nitrophenyl)propanoic acid. The key step is the mild phthalimidine synthesis by the double Mannich condensation of o-phthalaldehyde with ethyl 2-(4-aminophenyl)propanoate with use of 1,2,3-1H-benzotriazole and 2-mercaptoethanol as dual synthetic auxiliaries.
- Takahashi, Ichiro,Hirano, Etsushi,Kawakami, Teruki,Kitajima, Hidehiko
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p. 2343 - 2346
(2007/10/03)
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- High molecular weight prodrug derivatives of antiinflammatory drugs
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Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.
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- COBALT-CATALYZED LOW PRESSURE DOUBLE CARBONYLATION OF ARYL AND SECONDARY BENZYL HALIDES
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α-Ketoacids can be easily synthesized with satisfactory yields and selectivities by carbonylation of aryl halides and secondary benzyl halides under very mild conditions.The reactions are catalyzed by Co2(CO)8 in alcoholic solvents; the presence of a methyl source (dimethyl sulfate or methyl iodide) is necessary for the carbonylation of the aryl halides.Base, temperature and solvent have large effects on the course of the reaction.
- Francalanci, F.,Bencini, E.,Gardano, A.,Vincenti, M.,Foa, M.
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p. C27 - C30
(2007/10/02)
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- Novel process for preparing isoindoline derivatives
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A process for the preparation of an isoindoline derivative of the following general formula (II): STR1 wherein R2 is a hydrogen atom or lower alkyl group and X is a carboxyl group, carboalkoxy group, amide group or cyano group, which comprises cycling a benzylidene derivative of the following general formula (I) STR2 wherein R1 is a hydrogen atom or lower alkyl group, and R2 and X are as defined above, in the presence of a reducing agent such as sodium boron hydride. In one embodiment, the benzylidene derivative may be substituted by a reaction mixture containing the same, the reaction mixture being prepared by reacting o-phthalaldehydic acid or its ester with an aniline derivative.
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- Esters and amides containing the 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl moiety
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Compounds of the formula STR1 wherein each X, which may be identical or different from the other X, is oxygen or imino; R1 is hydrogen, fluorine, chlorine or bromine; R2 and R3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R2 and R3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one STR2 where R1, R2 and R3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.
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- Novel α-thio-alkanoic acid derivatives
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Novel α-thio-alkanoic acid derivatives and a process for their preparation. These novel compounds can be easily converted to useful medicines.
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- Aromatic acetic acid derivatives having sulfur atom at alpha-position and process for their preparation
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Aromatic acetic acid derivatives having a sulfur atom at the alpha-position, and a process for their preparation. Useful drugs can be produced from these derivatives.
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- Isoindoline derivatives for treating pain
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Isoindoline derivatives are disclosed, as for instance of the formula: STR1 and methods of preparation of these compounds, such as the reaction of o-cyano-benzylbromide with a compound of formula STR2 and subsequent saponification. The compounds possess analgesic and anti-inflammatory activity.
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- Tertiary aminoacids
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New α-(cyclic tert. aminophenyl)-aliphatic acids, e.g. those of the formula STR1 AND FUNCTIONAL DERIVATIVES THEREOF, ARE ANTI-INFLAMMATORY AGENTS.
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- Absorption, excretion and metabolism of a new analgesic and anti inflammatory drug K 4277 in rats, guinea pigs, rabbits and dogs
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Radioactive synthesis of indoprofen (K 4277; 2 [4 (1 oxo 2 isoindolinyl)phenyl]propionic acid) a new analgesic and antiinflammatory agent, is described. Administered orally in the rat, guinea pig, rabbit and dog, the 14C labelled drug was rapidly and entirely absorbed. In rat, plasma disappearance and excretion were slightly less rapid than in the other species, where radioactivity was almost completely excreted in 3 days. No relation was found between plasma protein binding, very high in all species, and peak plasma levels. Evidence of biliary excretion of the drug indoprofen in dog was ascertained following iv administration. The metabolic pathway in these species was similar and followed glucuronation and isoindoline ring hydroxylation in the 5 and 6 positions, but the quantitative distribution of unchanged drug and its metabolites in the excreta was very different.
- Goldaniga,Pianezzola,Valzelli
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p. 1603 - 1606
(2007/11/03)
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