cas 22246-18-0, 3,4-Dihydro-7-hydroxy-2(1H)-quinolinone

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An innovative approach for the synthesis of 7-hydroxyquinolin-2(1H)-one: A key intermediate of brexpiprazole
2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ) mediated oxidation of 7-hydroxy-1,2,3,4-tetrahydro-2-quinolinone has been prepared from 3-hydroxy aniline to obtain 7-hydroxyquinolin-2(1H)-one in aqueous media. Stoichiometric quantities of DDQ and THF provides a high out put of 7-hydroxyquinolin-2(1H)-one and reduces the consumption of organic solvents and discourages by-products. Overall advantage with this approach was reduce the time cycle and cost of the brexpiprazole intermediate.
Reddy, T Ram,Reddy, Desireddy Neha,Reddy, Bhimireddy Krishna,Kasturaiah, Chapala,Yadagiri, Kurra
p. 834 - 836
(2018)
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Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone
The invention belongs to the field of chemical engineering, and particularly relates to a preparation method of a brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone. According to the novel method for preparing the 7-hydroxy-1H-quinoline-2-ketone, DDQ is replaced with palladium on carbon, the obtained product is high in yield, few in impurity and easy to operate, the catalyst can be recycled, a target compound is synthesized through direct catalytic dehydrogenation, and the method has green atom economy and is suitable for industrial production.
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(2021/05/05)

Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist
Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].
Chaturvedi, Radha Nandan,Pendem, Krishnaiah,Patel, Vipul P.,Sharma, Mukta,Malhotra, Sunita
p. 2069 - 2084
(2018/08/22)

Method for synthesizing aripiprazole
The invention discloses a method for synthesizing aripiprazole. The method comprises making 4-halogenated-3-nitrophenol react with an ethylenation reagent under palladium catalysis conditions to obtain 3-nitro-4-vinylphenol; making the 3-nitro-4-vinylphenol and 1,4-dihalogenated butane reacting with alkali to obtain 4-(4-halobutoxy)-2-nitro-1-styrene; making the 4-(4-halobutoxy)-2-nitro-1-styreneand 1-(2,3-dichlorophenyl)piperazine salt reacting with the alkali to obtain 1-(2,3-dichlorophenyl)-4-(4-(3-nitro-4-vinylphenoxy)butyl)piperazine; making the 1-(2,3-dichlorophenyl)-4-(4-(3-nitro-4-vinylphenoxy)butyl)piperazine reacting with CO to form the aripiprazole. The method for synthesizing the aripiprazole has the total yield of up to 77% and is simple in post treatment.
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(2019/01/16)

Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins
The bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent selectivity over nonclass IV BRD proteins. Target engagement of BRPF1B and BRPF2 with 16 was demonstrated in nanoBRET and FRAP assays. The binding of 16 to BRPF1B was rationalized through an X-ray cocrystal structure determination, which showed a flipped binding orientation when compared to previous structures. We report studies that show 16 has functional activity in cellular assays by modulation of the phenotype at low micromolar concentrations in both cancer and inflammatory models. Pharmacokinetic data for 16 was generated in mouse with single dose administration showing favorable oral bioavailability.
Igoe, Niall,Bayle, Elliott D.,Tallant, Cynthia,Fedorov, Oleg,Meier, Julia C.,Savitsky, Pavel,Rogers, Catherine,Morias, Yannick,Scholze, Sarah,Boyd, Helen,Cunoosamy, Danen,Andrews, David M.,Cheasty, Anne,Brennan, Paul E.,Müller, Susanne,Knapp, Stefan,Fish, Paul V.
supporting information
p. 6998 - 7011
(2017/09/07)

Method for synthesizing aripiprazole using m-amino phenol as raw material
The present invention discloses a method for synthesizing aripiprazole using m-amino phenol as a raw material. The synthesis method comprises: step 1, performing a substitution reaction on the m-amino phenol and 3-methoxy propionyl chloride in an aqueous solution of a strong base; step 2, performing electrophilic substitution on the product obtained in the first step using boron trifluoride diethyl ether as a catalyst; step 3, performing a substitution reaction on the product obtained in the second step and 4-bromine-1-butyl iodide under catalysis of the strong base in solvent composed of DMSO, DMF and water; and step 4, performing a substitution reaction on the product obtained in the third step and 1-(2, 3-dichloro phenyl) piperazine under catalysis of the strong base in solvent composed of DMSO, DMF and water; Tert-butyl benzenesulfonic acid 4-chloro butyl ester and 7-hydroxy-3, 4-2 (1H) dihydroquinolinone are used for a substitution reaction. Since tert-butyl benzenesulfonyloxy and chlorine respectively in 1, 4-position carbon atoms in 4-bromine-1-butyl iodide have different substitution activity, iodine is preferably substituted by hydroxy, and in this way dimerized quinolinone by-products are reduced, thereby improving the purity of the product and ensuring the yield.
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(2016/10/08)

Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates
The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
Sharada,Satyanarayana Reddy,Sammaiah,Sumalatha
p. 7959 - 7966
(2013/09/23)

METHOD FOR PRODUCING A CROSS-COUPLING PRODUCT OF A BENZENOID DIAZONIUM SALT
The invention relates to a method for producing a cross-coupling product of a benzenoid dizonium salt according to the general formula (I), wherein the groups R1, R2, R3, R4, and R5 represent hydrogen, halogen, an alkyl, alkenyl, aryl, alkoxy, aryloxy, nitro, cyano, hydroxy, acetyl, and/or diazo groups independently of each, and X represents BF4, Cl, F, SO3CH3, CO2CH3, PF6, ClO2CH3, or CIO4, comprising the following steps: (a) providing a benzenoid amide, which with the exception of the diazo function has the same substituents R1, R2, R3, R4, and R5 as the benzenoid diazonium salt of the general formula (I), and hydrolytically cleaving the amide to form an amine or providing a corresponding amine, (b) diazotizing the amine thus obtained or provided with a nitrite, and (c) subsequently reacting the benzenoid diazonium salt with a coupling partner in the presence of a catalyst to form a cross-coupling product, wherein the coupling parter is represented by the general formula (II), R6, R7, and R8 are the same or different and represent hydrogen, carboxyalkyl groups, carboxyaryl groups, alkyl groups, aryl groups, alkoxy groups, aryloxy groups, wherein the groups can each contain Si, N, S, O, and or halogen atoms, or R6 and R7 with the double bound form an aromatic ring, which can be provided with R8 and one to four further substituents, independently of each other, selected from the group comprising a straight-chain or branched (C1-C6) alkyl group, a (C3-C7) cycloalkyl group, a straight-chain or branched (C1-C6) alkenyl group, a straight-chain or branched (C1-C6) alkyoxy group, halogen, the hydroxy group, an amino, di(C1-C6) alkylamino, nitro, acetyl, cyan, benzyl, 4-methoxybenzyl, 4-nitrobenzyl, phenyl, and 4-methoxyphenyl group and represents Y=H, —B(OR)2, —SnR3, —ZnR, —SiR3, or Mg (halogen), and wherein at least the steps (b) and (c) are performed without intermediate isolation of an intermediate product. According to said method, cross-couplings can be performed more simply and with improved yield without the hydroxyl group in aromatic reactants containing hydroxyl groups having to be provided with a protective group.
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Paragraph 0056; 0057; 0058; 0059; 0060; 0061

(2013/03/26)

Selective dual inhibitors of CYP19 and CYP11B2: Targeting cardiovascular diseases hiding in the shadow of breast cancer
Postmenopausal women are at high risk for cardiovascular diseases because of the estrogen deficiency. As for postmenopausal breast cancer patients, this risk is even higher due to inhibition of estrogens biosyntheses in peripheral tissue by the aromatase (CYP19) inhibitors applied. Because estrogen deficiency results in significantly elevated aldosterone levels, which are a major cause of cardiovascular diseases, dual inhibition of CYP19 and CYP11B2 (aldosterone synthase) is a promising treatment for breast cancer and the coinstantaneous cardiovascular diseases. By combination of important structural features of known CYP19 and CYP11B2 inhibitors, we succeeded in obtaining compounds 3 and 5 as selective dual inhibitors with IC50 values around 50 and 20 nM toward CYP19 and CYP11B2, respectively. These compounds showed also good selectivity toward CYP11B1 (selectivity factors (IC50 CYP11B1/IC 50 CYP11B2) around 50) and CYP17 (no inhibition).
Hu, Qingzhong,Yin, Lina,Hartmann, Rolf W.
supporting information
p. 7080 - 7089
(2012/11/07)

Synthesis of novel 3,4-dihydroquinolin-2(1H)-one guanidines as potential antihypertensive agents
Hydroxy-3,4-dihydroquinolin-2(1H)-ones (4a-c) were synthesized by intramolecular Friedel Craft alkylation of N-(methoxyphenyl)-3- chloropropionamides (3a-c), obtained by acylation of anisidine with chloropropionyl chloride. The hydroxy-3,4-dihydro quinolin-2(1H)- ones (4a-c) were treated with various dibromo alkanes under phase transfer catalyst conditions at room temperature to give bromoalkyloxy- 3,4-dihydroquinolin-2(1H)- ones (5a-l) which on further reaction with guanidine hydrochloride in dimethyl formamide afforded N-{4- [(2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)oxy]alkyl} guanidines (6a-l). These compounds were synthesized as potential antihypertensive agents.
Pai,Samel
experimental part
p. 1655 - 1660
(2012/01/06)

Mizoroki-heck reactions with 4-phenoldiazonium salts
Significantly better yields were achieved in Mizoroki-Heck reactions using 4-phenoldiazonium salts instead of their O-alkylated analogues under otherwise identical conditions. We found that a one-flask deacetylation-diazotation- precipitation sequence starting from paracetamol or acetanilides derived thereof provides a convenient access to the required diazonium tetrafluoroborates. The utility of these arylating agents in palladium-catalyzed C-C bond forming reactions was demonstrated for a one-flask-synthesis of the heterocyclic core of the drug aripiprazole. Notably, the diazonium salt formation from an acetanilide could be combined with two Pd-catalyzed steps in a one-flask sequence, without any exchange of solvents or isolation of intermediates.
Schmidt, Bernd,Hoelter, Frank,Berger, Rene,Jessel, Soenke
supporting information; experimental part
p. 2463 - 2473
(2010/12/25)

Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia
A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity.
Yan, Yinfa,Zhou, Ping,Rotella, David P.,Feenstra, Rolf,Kruse, Chris G.,Reinders, Jan-Hendrik,Neut, Martina van der,Lai, Margaret,Zhang, Jean,Kowal, Dianne M.,Carrick, Tikva,Marquis, Karen L.,Pausch, Mark H.,Robichaud, Albert J.
scheme or table
p. 2983 - 2986
(2010/08/06)

Preparation of 2-Quinolones by sequential heck reduction-cyclization (HRC) reactions by using a multitask palladium catalyst
One-pot sequential Heck reduction-cyclization (HRC) reactions leading to the synthesis of substituted 2-quinolones have been developed by using a heterogeneous or mixed homogeneous/heterogeneous multitask palladium catalyst with charcoal as a support. The whole sequence occurs under very mild conditions without the need for additives (ligand or base) by taking advantage of the high reactivity of aryldiazonium salts as "super electrophiles". Recycling experiments showed that the reused heterogeneous Pd°/C catalyst was not able to promote another HRC sequence but was, however, still highly active for hydrogenation, hydrodehalogenation, as well as hydrogenolysis reactions.
Felpin, Francois-Xavier,Coste, Jerome,Zakri, Cecile,Fouquet, Eric
experimental part
p. 7238 - 7245
(2010/03/25)

ACTIVATIBLE DYES
Novel, activatable dyes, such as photoactivatable dyes, e.g., oxazine dyes, are described. Some of the dyes are targeting dyes that can, e.g., target biomolecules, such as polypeptides, proteins, or nucleic acids. Upon activation, such as by irradiation, the novel dyes rapidly turn on their fluorescence and emit light, such as near-IR light with spatial and temporal precision.
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Page/Page column 13/24

(2009/04/25)

Synthesis of indolones and quinolones by reductive cyclisation of o-nitroaryl acids using zinc dust and ammonium formate
A novel protocol for the synthesis of indolone and quinolone derivatives from o-nitroaryl acids was developed using Zn and HCO2NH4 under supercritical fluid carbon dioxide (scCO2) medium. The process involves the reduction of the nitro group to an amino group followed by in situ cyclisation.
Dinesh, Bhima Reddy,Baba, A. Ramesha,Sankar, K. Udaya,Gowda, D. Channe
experimental part
p. 287 - 288
(2009/04/07)

ANTIDEPRESSANT HETEROARYL DERIVATIVES OF HETEROCYCLE-FUSED BENZODIOXANS
The invention provides compounds of the Formula: (I) that are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre- menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses. The compounds are able to block the recptake of serotonin and are modulators at brain 5HT1A serotonin receptors.
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Page/Page column 132-133

(2009/01/24)

A NOVEL PROCESS FOR PREPARATION OF ARIPIPRAZOLE AND ITS INTERMEDIATES
A process for the preparation of 7-hydroxy-3,4-dihydro carbostyril (II) by intramolecular Fridel-Craft alkylation of N-(3-methoxyphenyl)-3-chloropropionamide (I) in which an equivalent of N-(3-methoxyphenyl)-3-chloropropionamide (I) is contacted with a Lewis acid (e.g. aluminium chloride) in dimethyl acetamide (DMA), at an elevated temperature of from about 120°C to about 160°C, is provided. The process produces 7-hydroxy-3,4- dihydro carbostyril (II) in high yield and a high state of purity such that it may be used in subsequent .reaction towards the preparation of aripiprazole (IV). Thus 7-hydroxy-3,4- dihydro carbostyril (II) was treated with l-bromo-4-chlorobutane under phase transfer catalyst (PTC) conditions using solvents like acetone or n-butanol at temperature ranging 25°C to 45°C to afford 7-(4-chlorobutoxy)-3,4-dihydro carbostyril (III). The PTC conditions described in this patent afford 7-(4-chlorobutoxy)-3,4-dihydro carbostyril (III) in high purity and high yield with the corresponding dimmer formation is considerably low as compared with the other literature methods of preparing 7-(4-chlorobutoxy)-3,4- dihydro carbostyril (III). Compound (III) was treated with l-(2,3-dichlorophenyl)piperazine, at temperature ranging from 50°C to 100°C, and sodium iodide, potassium carbonate, dimethyl formamide (DMF) as a solvent to afford aripiprazole in high purity and high yield.
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Page/Page column 6

(2010/11/28)

Processes for preparing 7-hydroxy-3,4-dihydro-2(1H)-quinolinone and the use in aripiprazole preparation thereof
The present invention provides improved processes for preparing the intermediate 7-hydroxy-3,4-dihydro-2(1H)-quinolinone (7-HQ), which may be used in preparing the drug aripiprazole. Among these processes are included three efficient processes for preparing 7-hydroxy-3,4-dihydro-2(1H)-quinolinone comprising reacting N-(3-methoxyphenyl)-3-chloropropionamide with AlCl3 using novel reaction conditions thus obtaining a substantially pure product, which may be used in the subsequent steps for obtaining aripiprazole without further purification.
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Page/Page column 6

(2008/06/13)

Synthesis and bioactivity of aripiprazole derivatives
Ten aripirazole (CAS 129722-12-9) derivatives were prepared and examined for dopamine receptor antagonist activity. The structures of these newly synthesized compounds were confirmed by their elemental analyses and by IR, 1H-NMR and mass spectra. It was demonstrated that all the new compounds have dopamine receptor antagonist activity to a certain extent. Three compounds showed more potent activity than aripiprazole. ECV · Editio Cantor Verlag.
Ge, Hai-Xia,Wang, Li-Chen,Jiang, Zhen-Zhou,Ni, Sheng-Liang
p. 673 - 677
(2007/10/03)

PIPERAZINE DERIVATIVE RENIN INHIBITORS
Disclosed are piperazine derivatives, their manufacture and use as inhibitors of renin. Formula (I):
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Page 137-138

(2010/02/09)

Benzoamide piperidine containing compounds and related compounds
The present invention relates to certain benzoamide piperidine containing compounds and related compounds that exhibit activity as NK-1 receptor antagonists, (e.g., substance P receptor antagonists), to pharmaceutical compositions containing them, and to their use in the treatment and prevention of central nervous system disorders, inflammatory disorders, cardiovascular disorders, ophthalmic disorders, gastrointestinal disorders, disorders caused by helicobacter pylori, disorders of the immune system, urinary incontinence, pain, migraine, emesis, angiogenesis and other disorders.
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(2008/06/13)

Phenyl-oxo-tetrahydroquinolin-3-yl beta-3 adrenergic receptor agonists
This invention provides compounds of Formula I having the structure and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
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(2008/06/13)

Aluminium chloride-catalyzed intermolecular vs intramolecular friedel-crafts reaction of acrylanilides and 3-chloropropanamides
3-Phenylpropionanilide (4a) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl3/ benzene, compared with a yield of 39% by the 1,4-conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel-Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3-phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N-phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl3-catalyzed demethylation to form the ArOAlCl2 complex which decreased the availability of the π-electron in the N-phenyl aromatic system.
Chen, I.-Li,Wang, Tai-Chi,Chen, Yeh-Long,Tzeng, Cherng-Chyi
p. 155 - 162
(2007/10/03)

CARBAMYLPIPERAZINE COMPOUNDS
4-(3-Aryloxy-2-hydroxypropyl)piperazines bearing a carbamyl group in the 1-position are β-adrenergic blockers. A typical example is 1-carbamyl-4-{3-2-allyl-3-(2-carbethoxyaminoethyl)phenoxy!-2-hydroxypropyl} piperazine.
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(2008/06/13)