- Mild, General, and Regioselective Synthesis of 2-Aminopyridines from Pyridine N -Oxides via N -(2-Pyridyl)pyridinium Salts
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A synthesis of 2-aminopyridines from pyridine N-oxides via their corresponding N-(2-pyridyl)pyridinium salts has been demonstrated and investigated. The reaction sequence features a highly regioselective conversion of the N-oxide into its pyridinium salt
- Xiong, Hui,Hoye, Adam T.
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supporting information
p. 371 - 375
(2022/01/27)
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- Preparation of 1H-imidazo[4,5-c]quinolin-4-amines via 1H-imidazo[4, 5-c]quinolin-4-phtalimide intermediates
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The present invention provides process for the preparation of 4-amino-1H-imidazo[4,5-c]quinolines comprising the step of reacting a 1H-imidazo[4,5-c]quinolin-4-phthalimide with an amine selected from the group consisting of: alkylamine, aralkylamine, alkyldiamine, and aralkyldiamine.
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Page/Page column 5
(2008/06/13)
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- IMIQUIMOD PRODUCTION PROCESS
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The present invention provides a process for preparing highly pure 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod). The process preferably includes heating 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline of formula (II) with ammonia in a polar aprotic solvent at relatively moderate pressure to produce imiquimod, and optionally purifying the imiquimod. The process of the present invention can produce highly pure imiquimod in high yield.
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Page/Page column 2-3
(2008/12/07)
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- Imiquimod Production Process
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Provided is a process for producing highly pure 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod), which includes reacting 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline with a non-gaseous amine precursor. Also provided are methods for isolating highly pure imiquimod. Further provided are intermediates useful in the production of imiquimod, methods for producing such intermediates, and methods for obtaining imiquimod from such intermediates.
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Page/Page column 2; 4
(2008/12/07)
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- New process for the manufacture of 1H-imidazo [4,5-c]-quinoline ring systems
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The present invention relates to a new synthetic route to manufacture 1H-imidazo[4,5-c]-quinoline ring systems and to new corresponding intermediates. Said new intermediates are biaryl aminonitrile compounds of formula (II)
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Page/Page column 17
(2009/01/24)
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- Process for preparing Imiquimod
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The present invention provides a process for preparing 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (Imiquimod) of formula (I). The process comprises heating 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline of formula (II) with formamide, and optionally with bubbling of gaseous ammonia to afford Imiquimod of formula (I). According to the present invention, by using this process and novel purification methods, essentially as described herein, highly pure Imiquimod is obtained.
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Page/Page column 4
(2008/06/13)
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- Process for the preparation of imidazo[4,5-c]-quinolin-4-amines
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The present invention is a method for preparing a compound of the formula wherein R is hydrogen, C1 to C6 alkyl, C1 to C6 alkoxy or halo, R1 and R2 are independently hydrogen, C1 to C10 alkyl, C1 to C10 alkoxy, C3 to C10 cycloalkyl, C3 to C10 alkenyl, C5 to C10 cycloalkenyl, C2 to C10 alkynyl, C6 to C20 aryl or substituted C6 to C20 aryl and n is the integer 1 or 2 by reacting the corresponding N-oxide with an aqueous solution of ammonia and a C1 to C6 alkyl, C6 to C20 aryl or substituted C6 to C20 aryl chloroformate thereby forming said compound formula (1).
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Page/Page column 3-4
(2008/06/13)
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- A process for the purification of imiquimod
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Crystalline forms of imiquimod, a process for the preparation thereof and the use thereof in the purification of imiquimod.
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Page/Page column 3
(2008/06/13)
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- METHOD FOR MAKING 1-SUBSTITUTED 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE COMPOUNDS AND INTERMEDIATES THEREFOR
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The present invention concerns a method for manufacturing 1-substituted lfl-imidazo [4, 5-c] quinolin-4-amine compounds through their corresponding f ormamides . The invention also concerns new formamide intermediates.
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Page/Page column 9
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF SUBSTANTIALLY PURE 4-AMINO-1-ISOBUTYL-1H-IMIDAZO[4,5-C]-QUINOLINE (IMIQUIMOD)
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A process for preparation of Imiquimod comprising oxidation of 1-Isobutyl-1H-imidazo-[4,5-c]-quinoline (II) afforded 1-Isobutyl-1H- imidazo-[4,5-c]-quinoline-5-N-oxide(III) which is isolated in pure form as its hydrochloride salt (IV) followed by conversion to 4-chloro derivative(V) and conversion to corresponding 4-iodo derivative (VI) which is a novel intermediate. This novel intermediate is converted to imiquimod (VIII) and purified via its organic salt. The invention also relates to crystalline polymorphic forms of Imiquimod Maleate, Fumarate and Oxalate.
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Page/Page column 16
(2008/06/13)
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- A PROCESS FOR PREPARATION OF 4-AMINO-1-ISOBUTYL-1H-IMIDAZO[4,5-C]-QUINOLINE (IMIQUIMOD)
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A process for preparation of imiquimod comprising oxidation of 1-Isobutyl-1H-imidazo quinoline quinoline (II) afforded 1-Isobutyl-lH- imidazo-[4,5-c]-quinoline-5-N-oxide (III) which is isolated in pure form as its hydrochloride salt (IV) followed by conversion to 4-chloro derivative(V) and conversion to corresponding 4-iodo derivative (VI) which is a new intermediate. This new intermediate is convened to imiquimod (VIII) and purified via its novel maleate salt.
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Page/Page column 11-12
(2008/06/13)
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- Process for the preparation of Imiquimod
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A process for the preparation of Imiquimod and novel hydroxylamino and hydrazine derivatives, useful as intermediates in its preparation. The process includes the reaction of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline, of formula (I) with a compound of formula (II) [in-line-formulae]NH2—X??(II) [/in-line-formulae] wherein X is an —OR or —NR1R2 group, in which R is hydrogen, a C1-C6 alkyl, aryl-C1-C4 alkyl, aryl or —SO3H (sulfonic) group; and each of R1 and R2 is independently hydrogen, a C1-C6 alkyl, aryl-C1-C4 alkyl, aryl or —SO2R3 group, in which R3 is an aryl group and, if necessary, the reaction with a reducing agent.
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Page/Page column 3
(2008/06/13)
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- METHOD OF PREPARING 4-AMINO-1H-IMIDAZO(4,5-c)QUINOLINES AND ACID ADDITION SALTS THEREOF
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The present invention provides a method of preparing a 4-(arylmethyl)amino-1H--imidazo(4,5-c)quinoline of formula (4) by reacting an arylmethylamine of formula (3) with a 4-chloro-lH-imidazo(4,5-c)quinoline of formula (2). The present invention further provides a method of preparing an acid addition salt of formula (5) comprising the step of hydrolyzing a 4-(arylmethyl)amino- 1 H-imidazo(4,5-c)quinoline of formula (4) with a strong acid, HX The present invention further provides a method of preparing a 4-amino- 1H-imidazo(4,5-c)quinoline of formula (1) comprising the step of treating an acid 10 addition salt of formula (5) with a base.
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Page/Page column 26
(2008/06/13)
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- Synthesis and structure - Activity-relationships of 1H-imidazo[4,5-c] quinolines that induce interferon production
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1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.
- Gerster, John F.,Lindstrom, Kyle J.,Miller, Richard L.,Tomai, Mark A.,Birmachu, Woubalem,Bomersine, Shannon N.,Gibson, Shiela J.,Imbertson, Linda M.,Jacobson, Joel R.,Knafla, Roy T.,Maye, Peter V.,Nikolaides, Nickolas,Oneyemi, Folakemi Y.,Parkhurst, Gwen J.,Pecore, Sharon E.,Reiter, Michael J.,Scribner, Lisa S.,Testerman, Tracy L.,Thompson, Natalie J.,Wagner, Tammy L.,Weeks, Charles E.,Andre, Jean-Denis,Lagain, Daniel,Bastard, Yvon,Lupu, Michel
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p. 3481 - 3491
(2007/10/03)
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- A process for the preparation of imiquimod and intermediates thereof
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A process for the preparation of Imiquimod and novel hydroxylamino and hydrazine derivatives, useful as intermediates in its preparation.The process comprises the reaction of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline, of formula (I)???with a compound of formula (II)NH2-X??????(II)???wherein X is an -OR or -NR1R2 group, in which R is hydrogen, a C1-C6 alkyl, aryl-C1-C4 alkyl, aryl or -SO3H (sulfonic) group; and each of R1 and R2 is independently hydrogen, a C1-C6 alkyl, aryl-C1-C4 alkyl, aryl or -SO2R3 group, in which R3 is an aryl group and, if necessary, the reaction with a reducing agent.
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Page/Page column 5
(2008/06/13)
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- PREPARATION OF 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES VIA1H-IMIDAZO [4,5-C]QUINOLIN-4-PHTHALIMIDE INTERMEDIATES
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The invention provides 1H-imidazo(4,5-C) quinolin-4-phthalimide intermediates useful in the synthesis of 1H-imidazo(4,5-C) quinoline-4-amines, particularly Imiquimod. The invention further provides a method for making the intermediates and a method for making 1H-imidazo (4,5-C) quinoline-4-amines via the intermediates.
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- PREPARATION OF 1H-IMIDAZO [4,5-C] QUINOLIN-4-AMINES VIA NOVEL 1H-IMIDAZO [4,5-C] QUINOLIN-4-CYANO AND 1H-IMIDAZO [4,5-C] QUINOLIN-4-CARBOXAMIDE INTERMEDIATES
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The invention relates to a process for the synthesis of 1H-imidazo[4,5-c] quinoline 4-cyano and 1H-imidazo[4,5-c] quinoline 4- carboxamide intermediates useful in preparing 1H-imidazo[4,5-C] quinoline 4-amines, a process for preparing 1H-imidazo [4,5-C] quinoline 4-amines using such intermediates; and, to the 1H-imidazo[4,5-c] quinoline 4-cyano and 1H-imidazo[4,5-c] quinoline 4- carboxamide intermediates. More particularly, the invention relates to a process for the preparation of 1-isobutyl-1H-imidazo [4,5-C] quinoline 4-amine (Imiquimod) using two intermediates, 1-isobutyl-1H-imidazo[4,5-c]quinoline 4-cyano and 1-isobutyl-1H-imidazo[4,5-c]quinoline 4-carboxamide, and to the said intermediates.
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- Use of immidazoquinolinamines as adjuvants in dna vaccination
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The present invention relates to the use of a 1H-imidazo[4,5-c]-4-amine derivative as an adjuvant for use with nucleic acid vaccination.
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- Pharmaceutical formulation comprising an immune response modifier
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Pharmaceutical formulations comprising an immune response modifier (IRM) chosen from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazolo-quinolineamines, oxazolo-quinolinamines, thiazolo-pyridinamines, oxazolo-pyridinamines, imidazonaphthyridine amines, tetrahydroimidazonaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; and a hydrophobic, aprotic component miscible with the fatty acid are useful for the treatment of dermal associated conditions. Novel topical formulations are provided. In one embodiment, the topical formulations are advantageous for treatment of actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts.
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- Amide derivatives and intermediates for the synthesis thereof
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Novel compounds which are amide derivatives represented by general formula (I) and medicinal preparations containing the same having an eosinophilic infiltration inhibitory effect based on a potent interferon (α,γ)-inducing activity and an exellent percutaneous absorbability and being efficacious in treating allergic inflammatory diseases such as atopic dermatitis, various tumors and viral diseases. In said formula, each symbol has the following meaning: R1 and R2 : each lower alkyl, etc.; X and Y: independently representing each oxygen, NR4, CR5 etc. (wherein R4 and R5 independently represent each hydrogen, an aromatic group, etc.); Z: an aromatic ring or heterocycle; R3 : hydrogen, lower alkoxy, etc.; g, i and k: independently representing each an integer of from 0 to 6; h, i and l: independently representing each an integer of 0 or 1; m: an integer of from 0 to 5; and n: an integer of from 2 to 12.
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- Process for reparing imidazoquinolinamines
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A process for preparing 1H-imidazo?4,5-c!quinolin-4-amines is disclosed. The process involves reacting a 6H-imidazo?4,5-c!tetrazolo?1,5-a!quinoline with triphenylphosphine and hydrolyzing the product thereof.
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- Synthesis of the interferon-α inducer imiquimod by thermal electrocyclic reactions of 1- and 2-azahexatriene systems
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The interferon-α inducer imiquimod (1), possessing an imidazo[4,5- c]quinoline ring, has been newly synthesized by two routes on thermal electrocyclic reactions of 1- and 2-azahexatriene systems involving the imidazole 4,5-bond.
- Yoshioka, Haruyuki,Matsuya, Yuhji,Choshi, Tominari,Sugino, Eiichi,Hibino, Satoshi
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p. 709 - 714
(2007/10/03)
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- Process for preparing quinoline amines
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A process that involves reacting a 3-nitroquinoline-2,4-disulfonate with an amine or a substituted amine to selectively aminate at the 4-position to yield 1H-imidazo[4,5-c]quinolin-4-amines is disclosed.
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- Imidazo[4,5-c]quinolin-4-amines and processes for their preparation
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A process and intermediates for preparing 1-substituted-1H-imidazo[4,5-c]quinolin-4-amines. The process involves reacting a 1-substituted-1H-imidazo[4,5-c]quinoline-5N-oxide with an isocyanate and hydrolysing the product thereof. Also, a process for preparing the intermediates is disclosed.
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- 3-Amino or 3-nitro quinoline compounds which are intermediates in preparing 1H-imidazo[4,5-c]quinolines
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A process for the preparation of 1-substituted, 4-substituted-1H-imidazo[4,5-c]quinolines, intermediates in the preparation of such compounds, and processes for the preparation of such intermediates.
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- 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND ANTIVIRAL USE
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1H-Imidazo[4,5-c]quinolin-4-amines which are antivirals. Pharmacological methods of using such compounds and pharmaceutical compositions containing such compounds are also described
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