- Electrochemical Synthesis of Carbazoles by Dehydrogenative Coupling Reaction
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A constant current protocol, employing undivided cells, a remarkably low supporting electrolyte concentration, inexpensive electrode materials, and a straightforward precursor synthesis enabling a novel access to N-protected carbazoles by anodic N,C bond formation using directly generated amidyl radicals is reported. Scalability of the reaction is demonstrated and an easy deblocking of the benzoyl protecting group is presented.
- Kehl, Anton,Schupp, Niclas,Breising, Valentina M.,Schollmeyer, Dieter,Waldvogel, Siegfried R.
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p. 15847 - 15851
(2020/11/02)
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- Total synthesis of carbazole alkaloids
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A Suzuki-Miyaura cross coupling, followed by triphenylphosphine mediated Cadogan reductive cyclization sequence provided efficient access to a series of carbazole alkaloids. In the present work, this approach was applied to the total synthesis of mukonine, clauszoline K, koenoline, murrayanine, murrayafoline A, mukoeic acid, glycoborine, glycozolicine, mukolidine, mukoline, glycozoline, 3-methoxy-9H-carbazole-1-carboxylic acid methyl ester, (3-methoxy-9H-carbazol-1-yl)-methanol, 3-methoxy-9H-carbazole-1-carbaldehyde, 3-methoxy-9H-carbazole-1-carboxylic acid, 2-methyl-9H-carbazole and nonsteroidal anti-inflammatory drug (NSAID) carprofen and its derivatives.
- Bhatthula, Bharath kumar goud,Kanchani, Janardhan reddy,Arava, Veera reddy,Subha
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p. 874 - 887
(2019/01/11)
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- Carprofen and its intermediate synthesis method
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A synthesis of carprofen, (1) 2 - (3 - bromo - 4 - chlorophenyl) propionic acid and P-nitro aniline reaction, formula C - 1 as shown in the; (2) Type C - 1 as shown in the compound is subjected to reduction reaction, formula C - 2 as shown in the; (3) Type C - 2 shown compound is subjected to diazotization reaction, preparation formula B - 3 as shown in the and by-product B - 31 shown compound mixture; (4) Type B - 3 and the product of a compound represented by B - 31 shown compound mixture through processing formula B - 3 illustrated compound; (5) Type B - 3 as shown in the reaction shown in formula A carprofen;
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- Carprofen and its intermediate synthesis method
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A synthesis of carprofen: (1) 4 - chloroaniline and 2 - iodo - 4 - bromo-chlorobenzene reaction, generating M - 1 illustrated compound. (2) Type M - 1 as shown in the after reaction, generating M - 2 shown compound. (3) Type M - 2 by the reaction of a compound of, formula M - 3 illustrated compound. (4) Type M - 3 through the reaction of a compound represented by formula M - 4 illustrated compound. (5) The formula M - 4 through the reaction of a compound represented by formula M - 5 illustrated compound. (6) Type M - 5 as shown in the reaction shown in formula A carprofen. .
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- Carprofen and its intermediate synthesis method
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A synthesis of carprofen, comprising the following steps: (1) 2 - (3 - chloro - 4 - nitrophenyl) propionic acid and to P-chloroaniline reaction, formula A - 1 as shown in the; (2) Type A - 1 shown compound is subjected to reduction reaction, formula A - 2 illustrated compound; (3) Type A - 2 shown through the diazo coupling reaction compound, a compound represented by formula A preparation, and by-product A - 3 illustrated compound; (4) Steps (3) to obtain the compound of formula A shown and by-product A - 3 shown compound mixture through purification treatment, to obtain not comprising by-product A - 3 of formula A shown carprofen.
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- Carprofen and its intermediate synthesis method
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A synthesis of carprofen: (1) 4 - [...] and 2 - chloro - 5 - bromophenyl reaction, generating M - 1 illustrated compound. (2) Type M - 1 as shown in the after reaction, generating M - 2 shown compound. (3) Type M - 2 by the reaction of a compound of, formula M - 3 illustrated compound. (4) Type M - 3 through the reaction of a compound represented by formula M - 4 illustrated compound. (5) The formula M - 4 through the reaction of a compound represented by formula M - 5 illustrated compound. (6) Type M - 5 as shown in the reaction shown in formula A carprofen. .
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Paragraph 0025; 0052; 0053; 0054; 0055; 0056; 0057
(2019/05/22)
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- Carbazole compound, and synthesis method and application of compound
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The invention discloses a carbazole compound represented by a formula (2) and a synthesis method of the compound. A high-iodine salt is taken as a reaction raw material, and under the action of an inorganic nitrogen reagent, an additive, a base and a metal catalyst, a reaction is carried out in a solvent under a condition of 80-150 DEG C to obtain various carbazole compounds. According to the method provided by the invention, nitrogen atoms are introduced in a later period, so that the non-compatibility of nitrogen heterocyclic rings to the reaction conditions such as the metal catalyst and the like in an early reaction period is avoided. In addition, two aryl groups in the high-iodine salt are fully utilized, so that the atomic economic efficiency of the method provided by the present invention is fully exhibited. The carbazole compound prepared by the method provided by the invention can be further applied to the synthesis of non-steroidal anti-inflammatory drug carprofen.
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Paragraph 0101; 0103
(2018/06/15)
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- Nitrogen-Iodine Exchange of Diaryliodonium Salts: Access to Acridine and Carbazole
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A nitrogen-iodine exchange protocol of diaryliodonium salts with sodium azide salt is developed for general construction of significant functional acridines and carbazoles, in which introduction of nitrogen at a late stage was successfully established avoiding heteroatom incompatibility. Inorganic sodium azide served as the sole nitrogen atom source in this transformation. The diversiform functional acridines and carbazoles were comprehensively achieved through annulated diaryliodonium salts, respectively. Notably, Acridine orange (a fluorescent indicator for cell lysosomal dye) and Carprofen (a nonsteroidal anti-inflammatory drug) were efficiently established through this protocol.
- Wang, Ming,Fan, Qiaoling,Jiang, Xuefeng
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p. 216 - 219
(2018/01/17)
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- Selective aryne formation via Grob fragmentation from the [2+2] cycloadducts of 3-triflyloxyarynes
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A chemoselective ring-opening protocol of the formal [2+2] cycloadducts of 3-triflyloxyarynes was developed to generate 2,3-aryne intermediate via Grob fragmentation. A variety of 1,3-di- and 1, 2, 3-trisubstituted arenes could be readily accessed through this [2+2] cycloaddition-2,3-aryne formation sequence. The regioselectivity in these transformations originates from the steric repulsion of the aliphatic chain.
- Shi, Jiarong,Xu, Hai,Qiu, Dachuan,He, Jia,Li, Yang
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supporting information
p. 623 - 626
(2017/05/15)
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- Synthetic Processes of Carprofen
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Methods and intermediates for the synthesis of carprofen and its derivatives starting from cyclohexanone are disclosed.
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Paragraph 0083
(2016/11/24)
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- Isolation and identification of an unusual impurity in an intermediate of Rimadyl (carprofen)
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The isolation and identification of an unknown process related impurity in a key intermediate of Rimadyl (carprofen) is described. The structure of the unknown was evaluated by NMR spectral analysis and eventually confirmed by single crystal X-Ray. A re-slurry in warm acetic acid was found to reduce the level of the unknown to an acceptable level.
- Tucker, John L.,DeVries, Keith M.,Hammen, Philip D.,Rose, Peter R.,Raymer, Brian K.,Rescek, Diane
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p. 1681 - 1688
(2007/10/03)
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- Syntheses of Carprofen, A Carbazole-Based Nonsteroidal Anti-Inflammatory Agent
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Syntheses of carprofen (6) have been achieved by two approaches from carbazole (11).In one, 2,9-diacetylcarbazole (12) and 2-acetylcarbazole (13) were chlorinated with trichloroisocyanuric acid (15) to give the 6-chloro derivatives (16) and (17), respectively.Reduction of 16 with NaBH4, followed by acetylation, cyanide displacement, and hydrolysis afforded 6 in 73percent yield from 16.Alternatively, 17 was converted into its trimethylsilyloxy cyanohydrin derivative (27), which was reduced with SnCl2 and hydrolysed to give 6 in 75percent yield from 17.In the other approach, the ketone (18), derived by a Friedel-Crafts acylation of 9-acetylcarbazole with 2-chloropropanoyl chloride followed by chlorination with 15, was converted into the hydroxyketal (28) with methanolic NaOMe.Mesylation of 28, followed by a modified Favorskii rearrangement and hydrolysis gave 6 in 73percent yield from 18.
- Manchand, Percy S.,Coffen, David L.,Belica, Peter S.,Wong, Frederick,Wong, Harry S.,Berger, Leo
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p. 833 - 846
(2007/10/02)
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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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- Derivatives of antiphlogistically effective carboxylic acids, their preparation and medicinal use
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Compounds of Formula I STR1 wherein R1 is the residue of an antiphlogistically effective carboxylic acid of the formula R1 COOH, n is an integer 1, 2, or 3, and X is oxygen, sulfur, or optionally alkylated nitrogen have valuable antiinflammatory activity.
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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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- Process of making 6-chloro-α-methyl-carbazole-2-acetic acid
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The aromatization of (6-chloro-1,2,3,4-tetrahydro-2-carbazolyl)-methyl-malonic acid dialkyl ester, utilizing chlorine and subsequent conversion of the resulting product to 6-chloro-α-methyl-carbazole-2-acetic acid by hydrolysis and decarboxylation are described.
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- Carbazole methyl malonates
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A process for the preparation of α-methyl-carbazole-2-acetic acids, which comprises reacting an α-methyl-3-oxocyclohexane malonic acid di-lower alkyl ester with a substituted phenylhydrazine, and thereafter sequentially oxidizing and hydrolyzing the reaction product to obtain the desired acid, is described.
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- Hydroxy methyl carbazole acetic acid and esters
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A process for the preparation of 6-chloro-α-methylcarbazole-2-acetic acid from 6-chloro-α-hydroxy-α-methylcarbazole-2-acetic acid and/or 6-chloro-α-methylene-2-carboxylic acid, is described. The preparation of intermediates, such as, 6-chloro-α-hydroxy-α-methylcarbazole-2-acetic acid and lower alkyl carbazole-2-oxalate, inter alia, is also described.
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