- Preparation method 6 -hydroxy -3-4 - dihydro -2 (1H)-quinolone (by machine translation)
-
HCl is added to the reaction solvent N, N - dimethylacetamide, HCl is added, solid matter is precipitated, filtered 2, the filter cake is washed 6 - times with ethanol, and then the 6 - residual solvent residue is 1 - 3 hours removed by -3 drying to 4 - obtain -2 the final product -3 hydroxyl 4 - 3 -2 dihydro 4 - 3 - (1H)-quinolonecarboxylic acid, N, N-(4 - 20 - 30 °C methoxyphenyl 0.05 - 0.2) propionamide. 1 is added 1H to the reaction solvent N, N-dimethylacetamide, and then the solvent is evaporated. The ionic liquid catalyst is high in thermal stability and catalytic performance, high in product yield, simple in reaction steps, easy to control and suitable for industrial production characteristics. (by machine translation)
- -
-
Paragraph 0014; 0023-0026
(2020/07/08)
-
- Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
-
Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
- Li, Yushu,Wong, Luet L.
-
supporting information
p. 9551 - 9555
(2019/08/06)
-
- Preparation method of 6-hydroxy-3,4-dihydro-2(1H)quinolinone
-
The invention belongs to the field of preparation of intermediates in chemical engineering, and particularly relates to a preparation method of 6-hydroxy-3,4-dihydro-2(1H)quinolinone. The preparationmethod comprises the following steps of using aniline and 3-chloropropionyl chloride as raw materials; performing cyclization, nitrification, reduction and diazotization hydrolysis, so as to synthesize the target product, namely 6-hydroxy-3,4-dihydro-2(1H)quinolinone. The preparation method has the advantages that the reaction conditions are mild, the cost is reduced, and the yield rate is increased.
- -
-
-
- Synthesis method of 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone
-
The invention provides a synthesis method of 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone. The synthesis method comprises the following steps: 1) taking p-alkoxyaniline as a raw material to react with 3-chloro-propionyl chloride, so as to prepare N-(4-alkoxyphenyl)-3-chloropropene amide; 2) dissolving the N-(4-alkoxyphenyl)-3-chloropropene amide obtained by step 2) into an organic solvent and adding acatalyst palladium chloride; raising the temperature to 100 to 110 DEG C under the pressure of 3 to 5kg, and carrying out heat preservation and reaction for 3 to 4h; after cooling to room temperature, filtering; spinning and drying filtrate to remove the organic solvent, so as to obtain a 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone crude product; 3) recrystallizing the 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone crude product obtained by step 3), de-coloring and filtering to obtain an off-white color solid 6-hydroxyl-3,4-dihydro-2(1H)-quinolinone. The synthesis method has the advantages of simplicity in operation, high yield and lower cost.
- -
-
Paragraph 0033; 0034
(2018/09/08)
-
- Preparation method of cilostazol
-
The invention discloses a preparation method of cilostazol and belongs to the field of medicines. The preparation method comprises the following steps: firstly, reacting 4-methoxyaniline with 3-chloropropionyl chloride in the presence of a solvent or no solvent; after a TLC (thin layer chromatography) detecting reaction is finished, adding aluminum trichloride into a system, and carrying out temperature raising reaction for 1 to 16 hours to obtain 6-hydroxy-3,4-dihydroquinoline-2-keto; secondly, in the presence of alkali, carrying out heating reaction on the 6-hydroxy-3,4-dihydroquinoline-2-keto obtained in the first step and 5-(4-chlorobutyl)-1-cyclohexanyl tetrazole in normal propyl alcohol to obtain the cilostazol. The high-purity cilostazol can be obtained by adopting the method disclosed by the invention; the preparation method has the advantages of few steps of the whole synthetic route, high yield, low cost, less wastewater and suitability for industrial production.
- -
-
Paragraph 0039-0040; 0043-0044; 0046-0047; 0049-0050; 0052
(2018/01/03)
-
- 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)
-
- Synthesis of related substances of cilostazol
-
The impurities in API of cilostazol were detected by LC/MS during the process development. The structures of two impurities 6 and 7 and the related formation mechanisms were proposed. Synthesis of 6 and 7 was conducted for confirmation of the speculated structures.
- Zheng, Jin,Liu, Zheng,Dai, Yiru,Zhao, Qingjie,Shen, Jingshan
-
scheme or table
p. 189 - 195
(2009/05/07)
-
- 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)
-
- Synthesis and anticonvulsant activity of 1-substituted-7-benzyloxy-4,5- dihydro-[1,2,4]triazolo[4,3-a]quinoline
-
Starting from 6-hydroxy-3,4-dihydro-1H-quinoline-2-one, a series of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines was synthesized and their structures were characterized using IR, 1H-NMR, MS, and elemental analysis techniques. Anticonvulsant activity was evaluated in the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scMet) test, and rotarod neurotoxicity test. The most active compound was 7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline 4a. Its ED50 in the MES and scMet tests was 17.3 and 24mg·kg-1, respectively. The safest compound was 4g, 1-phenyl-7-benzyloxy-4,5-dihydro-[1,2, 4]triazolo[4,3-a]quinoline, with TD50 and protective index (PI) (PI=TD50/ED50) values of greater than 300mg·kg -1 and 13, respectively. The PI value of compound 4g was better than that of most marketed drugs. Structure-activity relationships are also described in this paper.
- Cui, Li-Jing,Xie, Zhi-Feng,Piao, Hu-Ri,Li, Gao,Chai, Kyu-Yun,Quan, Zhe-Shan
-
p. 1216 - 1220
(2007/10/03)
-
- SUBSTITUTED BENZOLACTAM COMPOUNDS
-
This invention relates to compounds of general formula (I): or a pharmaceutically acceptable salt thereof, W, T, Y, X, Q, R, R, and R are defined herein. This invention also relates to compounds of formula (I), depicted above, wherein Y is -NH-; T is (2S,3S)-2-phenylpiperidin-3-yl, where the phenyl group of said (2S, 3S)-2-phenylpiperidine-3-yl may optionally be substituted with fluoro; Q is oxygen and is double bonded to the carbon atom to which it is attached, X is methoxy or ethoxy, R is hydrogen, methyl or halo-C1-C2 alkyl, W is methylene, ethylene or vinylene; R and R are independently hydrogen or methyl, or one of R or R may be hydroxy, when W is ethylene, R and R are both methyl, when W is methylene, and R and R are both hydrogen, when W is vinylene. The invention is further directed to methods of treating various CNS and other disorders using said compounds and pharmaceutical compositions thereof.
- -
-
-
- Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5α-reductase 1
-
New 5α-reductase 1 (5αR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5αR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the 1C50 values ranging from 8.1 to 1050 nM. The construction of this homogeneous set of molecules allowed a 3D QSAR study. In particular, comparative molecular field analysis (CoMFA) was used to correlate the potency of the inhibitors with their physicochemical features. Highly accurate evaluations of the atomic point charges were carried out by means of quantum chemical calculations at the DFT/B3LYP level of theory followed by the RESP fitting procedure. It turned out that increasing the reliability of electrostatic parameters greatly affected the statistical results of the QSAR analysis. The 3D QSAR model proposed could be very useful in the further development of 5αR-1 inhibitors, which are suitable candidates to be evaluated as drugs in the treatment of 5αR-1 related diseases such as acne and alopecia in men and hirsutism in women.
- Occhiato, Ernesto G.,Ferrali, Alessandro,Menchi, Gloria,Guarna, Antonio,Danza, Giovanna,Comerci, Alessandra,Mancina, Rosa,Serio, Mario,Garotta, Gianni,Cavalli, Andrea,De Vivo, Marco,Recanatini, Maurizio
-
p. 3546 - 3560
(2007/10/03)
-
- Substituted benzolactam compounds
-
This invention relates to compounds of the general formula (1): or a pharmaceutically acceptable salt thereof, W, T, Y, X, Q, R1, R2, and R3 are defined herein. This invention also relates to compounds of the formula I, depicted above, wherein Y is —NH—; T is (2S,3S)-2-phenylpiperidin-3-yl, where the phenyl group of said (2S, 3S)-2-phenylpiperidine-3-yl may optionally be substituted with fluoro; Q is oxygen and is double bonded to the carbon atom to which it is attached, X is methoxy or ethoxy, R1 is hydrogen, methyl or halo-C1-C2 alkyl, W is methylene, ethylene or vinylene; R2 and R3 are independently hydrogen or methyl, or one of R2 or R3 may be hydroxy, when W is ethylene, R2 and R3 are both methyl, when W is methylene, and R2 and R3 are both hydrogen, when W is vinylene. The invention is further directed to methods of treating various CNS and other disorders using said compounds and pharmaceutical compositions thereof.
- -
-
-
- Introduction of a hydroxy group at the para position and N-iodophenylation of N-arylamides using phenyliodine(III) bis(trifluoroacetate)
-
The reaction of anilides with phenyliodine(III) bis(trifluoroacetate) (PIFA) in trifluoroacetic acid (TFA), TFA-CHCl3, or hexafluoroisopropyl alcohol (HFIP) is described. When the acyl group of the anilide is highly electronegative, such as trifluoroacetyl, or the phenyl group is substituted with an electron-withdrawing group, the 4-iodophenyl group is transferred from PIFA to the amide nitrogen to afford acetyldiarylamines. On the other hand, when the acyl group contains an electron-donating function, such as 4-methoxyphenyl, or the phenyl group is substituted with an electron-donating group, a trifluoroacetoxy group is transferred to the para position of the anilide aromatic ring. This group is hydrolyzed during workup to produce the corresponding phenol.
- Itoh, Naoki,Sakamoto, Takeshi,Miyazawa, Etsuko,Kikugawa, Yasuo
-
p. 7424 - 7428
(2007/10/03)
-
- Processes for preparing 6-hydroxy-3,4-dihydroquinolinone, cilostazol and N-(4-methoxyphenyl)-3-chloropropionamide
-
A process for preparing 6-hydroxy-3,4-dihydroquinolinone by intramolecular Friedel-Crafts alkylation of N-(4-methoxyphenyl)-3-chloropropionamide in which an equivalent of N-(4-methoxyphenyl)-3-chloropropionamide is contacted with a Lewis acid in DMSO or a high boiling amide or amine at an elevated temperature of from about 150° C. to about 220° C. is provided. The process produces 6-HQ in high yield and a high state of purity such that it may be used in subsequent reactions toward the preparation of cilostazol without intermediate purification. A process for preparing cilostazol from 6-hydroxy-3,4-dihydroquinolinone prepared by the process and improved processes for preparing N-(4-methoxyphenyl)-3-chloropropionamide are also provided.
- -
-
-
- 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)
-
- A Simple Synthesis of 5-Methoxyindole and 5-Methoxy-2-oxindole
-
1-Methoxy- and 1-hydroxy-2-oxindoles rearranged in acidic solution to 5-substituted 2-aminophenylacetic acid derivatives which were cyclized to the corresponding 2-oxindoles with heating.The synthesis of 5-methoxyindole from 5-methoxy-2-oxindole was also described.
- Sakamoto, Takeshi,Hosoda, Isao,Kikugawa, Yasuo
-
p. 1279 - 1281
(2007/10/02)
-
- 3-[2-(4-Anisidino)phenyl]-1-phenyl-1-propiophenones and propanols
-
The invention relates to novel 1-(4-R1 O-phenyl)-2-(4-R2 -phenyl)-6-R3 -1,2,3,4-tetrahydroquinolines having anti-fertility and hypocholesterolemic activities, to their preparation, and to novel intermediates therefor.
- -
-
-
- Certain 1,2-diphenyl-1,2,3,4-tetrahydroquinoline compounds
-
The invention relates to novel 1-(4-R1 O-phenyl)-2-(4-R2 -phenyl)-6-R3 -1,2,3,4-tetrahydroquinolines having antifertility and hypocholesterolemic activities, to their preparation, and to novel intermediates therefor.
- -
-
-