Category: 363-51-9

363-51-9,Some common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, molecular formula is C6H5ClFN, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

a) To a stirred suspension of (A7) as obtained from example 5 (60.0 g, 126 mmol) in acetonitrile (180 ml.) was added pyridine (35.6 ml_, 440 mmol) and 2-chloro-6-fluoroaniline (27.4 g, 188 mmol, CAS-no. 363-51-9 obtained from Combiblocks, product code OS-7812; alternatively a preparation of 2-chloro-6-fluoroaniline is described in US 4,089,958, example XVIII) at 22C. The cloudy solution was cooled to 0-5C and phosphoryl chloride (21.2 g, 138 mmol) was added over a period of 10 min. The reaction mixture was stirred for 1 h resulting in a clear solution. Methanol (360 ml.) and 85% phosphoric acid (12.8 ml_, 189 mmol) were added and the mixture was heated to 60C for 2 h. (0796) The reaction solvent was partially removed by distillation (95C bath, 64-72C internal temperature) to give 420 ml. distillate. The distillation residue was slowly cooled to 22C and stirred for 16 h. The resulting suspension was cooled to 0-5C and stirred for additional 2 h. The solid was isolated, washed two times with 2-propanol (30 ml.) and dried in vacuum at 50C for 16 h to give crude product Compound (I) as a white solid (55g, 106 mmol) in 84% yield. (0797) HPLC (method 1 ): Rt = 2.81 min (> 98% area) (0798) b) The reaction product (30.0 g, 57.6 mmol) was further purified by suspension in anhydrous ethanol (450 ml.) and heating to 60C. The resulting clear solution was filtered, the filter cake was washed two times with hot anhydrous ethanol (30 ml.) and the filtrate was concentrated by distillation of solvent (270 ml. distillate) at 100C bath temperature. The solution was cooled to 50C, seeded (I) (0.3 g), and cooled stepwise to 0-5C over 4h. The precipitated solid was isolated, washed two times with anhydrous ethanol (15 ml.) and dried in vacuum at 50C for 16h to give Compound (I) as a white solid (25.7 g, 49.3 mmol) in 86% yield from crude (0799) Compound (I). (0800) HPLC (method 1 ): Rt = 2.81 min (> 99% area) (0801) 1H NMR (400 MHz, DMSO-d6) d ppm 1.29 (t, J=7.15 Hz, 3 H) 1.45 (d, J=6.36 Hz, 3 H) 3.80 (q, J= 7.09 Hz, 2 H) 4.44 – 4.55 (m, 2 H) 5.36 (dt, J=12.78, 6.33 Hz, 1 H) 5.80 (t, J= 5.75 Hz, 1 H) (0802) 7.30 – 7.47 (m, 3 H) 7.50 – 7.66 (m, 2 H) 10.05 (s, 1 H) (0803) LCMS (method 1 ): Rt = 0.90 min; MS (ESIpos): m/z = 521 (M+H)+

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 363-51-9, its application will become more common.

Reference:
Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; HASSFELD, Jorma; GRADL, Stefan, Nikolaus; RUBENBAUER, Philipp; VAN DER HAAS, Henricus, Nicolaas, Sebastian; GIELING, Reinerus, Geradus; (127 pag.)WO2019/197239; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

363-51-9, name is 2-Chloro-6-fluoroaniline, belongs to chlorides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 363-51-9

To a solution of 392 mg (0.890 mmol [calculation value with the purity defined as 100%]) of ethyl 5-(chioro- carbonyl)-6,6-dimethyl-3-[1 -(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)- carboxylate synthesized in the same way as in Reference Example 4 in 2.5 ml of 1,4-dioxane, 0.60 ml (3.4 mmol) of DIPEA and 807 mg (5.54 mmol) of 2-chloro-6-fluoroaniline were added at room temperature in a nitrogen atmosphere, reacted at 1000 C. for 1 hour with stirring, and then reacted at 130 C. for 0.5 hours and further at 150 C. for 2 hours in a microwave reaction apparatus. Subsequently, 0.50 ml (4.6 mmol) of N,N-dimethylethane-1 ,2-diamine was added thereto at room temperature and then reacted at room temperature for 1.5 hours with stirring.10718] After completion of the reaction, ethyl acetate was added to the reaction solution, followed by washing with a 5% aqueous potassium bisulfate solution. After separation into an organic layer and an aqueous layer, the aqueous layer was subjected to extraction twice with ethyl acetate. The whole organic layer thus obtained was dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to preparative column chromatography (apparatus 2, DIOL silica gel, elution solvent: n-hexane:ethyl acetate=80:20-65:35-50:50 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. The obtained concentration residue was subjected to preparative column chromatography (apparatus 2, silica gel, elution solvent: dichloromethane_methanol=100:0 99:1-98:2-97:3 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure to obtain a white solid (approximately 70 mg). The obtained solid was subjected to preparative column chromatography (apparatus 3, ODS silica gel, elution solvent: acetonitrile: 1 mM aqueous dipotassium biphosphate solution=50:50-80:20 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure, followed by the distilling oil of acetonitrile. The obtained concentration residue was subjected to extraction three times with ethyl acetate, and subsequently, the whole organic layer was washed with saturated saline, then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained concentration residue was dissolved in ethyl acetate, then n-hexane was added thereto, and the deposited solid was collected by filtration, washed with n-hexane, and then dried under reduced pressure to obtain 57.1 mg of the title compound (yield: 13% [calculation value with the purity of the starting material defined as 100%]) as a white solid.10719] Mass spectrum (CI, mlz): 478 [M+1].10720] ?H-NMR spectrum (400 MHz, DMSO-d5) oe: 12.27 & 11.69 (br s, total 1H), 9.64-9.54 (m, 1H), 8.09-7.89 (m, 1H), 7.38-7.19 (m, 3H), 4.69-4.52 (m, 2H), 2.56-2.39 (m, 2H), 2.28-2.13 (m, 2H), 1.93-1.73 (m, 2H), 1.70-1.54 (m, 6H), 0.15-0.04 (m, 9H).

Statistics shows that 363-51-9 is playing an increasingly important role. we look forward to future research findings about 2-Chloro-6-fluoroaniline.

Reference:
Patent; UBE INDUSTRIES, LTD.; IWASE, Noriaki; AGA, Yasuhiro; USHIYAMA, Shigeru; KONO, Shigeyuki; SUNAMOTO, Hidetoshi; MATSUSHITA, Takashi; OGI, Sayaka; UMEZAKI, Satoshi; KOJIMA, Masahiro; ONUMA, Kazuhiro; SHIRAISHI, Yusuke; OKUDO, Makoto; KIMURA, Tomio; (165 pag.)US2018/186818; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 363-51-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 363-51-9, name is 2-Chloro-6-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 2-chloro-6-fluorobenzenamine (5.0 g, 34 mmol) in chlorobenzene (52 mL) was added carbonothioic dichloride (thiophosgene) (5.1 g, 45 mmol) and DMF (0.27 mL). The reaction mixture was refluxed for 2 h and then concentrated to leave the title compound as a brown oil (6.15 g), which was used in Step C without further purification. ¾ NMR delta 7.18 (m, 2H), 7.07 (m, 1H).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 2-Chloro-6-fluoroaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; LONG, Jeffrey, Keith; GREGORY, Vann; GUTTERIDGE, Steven; TAGGI, Andrew, Edmund; BEREZNAK, James, Francis; WO2012/31061; (2012); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 363-51-9, name is 2-Chloro-6-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows., Safety of 2-Chloro-6-fluoroaniline

To a solution of 2-chloro-6-fluoro aniline (3.0 g, 19.35 mmol) in DCM (10 mL), N- ethyl di-isopropyl amine (8.0 g, 64.00 mmol) was added. The reaction mass was stirred at RT for 30 minutes. The reaction mass was cooled at 0C and drop-wise thiophosgene (5.01 g, 43.47 mmol) was added to the reaction mixture. The reaction mass was stirred RT for 3-4 h. After completion of reaction, the reaction mass was diluted with DCM and purified by using column chromatography to afford 1.0 g of desired title product. 1H NMR (DMSO-d6): delta 7.26 (m, 2H), 7.06 (t, J= 9.6Hz, 1H).

According to the analysis of related databases, 363-51-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLENMARK PHARMACEUTICALS S.A.; GHARAT, Laxmikant Atmaram; MUTHUKAMAN, Nagarajan; DESHMUKH, Sanjay; KHAIRATKAR-JOSHI, Neelima; KATTIGE, Vidya Ganapati; WO2013/153535; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 363-51-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 363-51-9 name is 2-Chloro-6-fluoroaniline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To 2-chloro-6-fluoroaniline (24.8 g, 165 mmol) in HOAc (90 mL) is added Ac2O (18 mL, 189 mmol) and the mixture is stirred at 90 C. for 1 h. After cooling to rt H2O is added and the mixture is neutralized with 2 M NaOH solution with stirring. The aqueous layer is extracted twice with DCM. The combined organic layer is washed with semi-saturated NaHCO3 solution and brine, dried over MgSO4 and evaporated to give the acetanilide which is used without further purification

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-6-fluoroaniline, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2012/322803; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 363-51-9,Some common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, molecular formula is C6H5ClFN, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

General procedure: A Schlenk tube was charged with Oxone (0.398 g, 0.648mmol) and trifloroacetic acid (0.099 mL, 1.296 mmol) in anhydrous dioxane (2 mL) under argon. To this mixture was added 2-fluoroaniline (0.06 g, 0.54 mmol), and the reaction mixture was heated to 90 C under argon until starting material was consumed. As the reaction progressed, the color turned from lightred to dark red. The mixture was then cooled to room temperature and washed with a saturated aqueous sodium bicarbonate.The mixture was extracted with EtOAc (2 × 20 mL) and the combined organic layers were dried over Na2SO4. After filtering andremoval of the solvent under reduced pressure in vacuo, theresidue was purified by silica gel (100-200 mesh) column chromatography(hexane-EtOAc, 9:1), to afford a pale-brown solid(65%) of 2-hydroxy-N-trifluoroacetanilides from 2-fluoroaniline(2a).

The synthetic route of 363-51-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Venkateswarlu, Vunnam; Balgotra, Shilpi; Aravinda Kumar; Vishwakarma, Ram A.; Sawant, Sanghapal D.; Synlett; vol. 26; 9; (2015); p. 1258 – 1262;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. HPLC of Formula: C6H5ClFN

Example 4b N-(2′-Chloro-6′-fluoro-phenyl)-4-methylaniline A solution of 3.91 g 2-chloro-6-fluoroaniline in 4 nm of tetrahydrofuran and 35 ml of chlorobenzene is cooled down to -40 to -45 C. At this temperature, 5.09 g of titanium tetrachloride is added to the solution, followed by the addition of 5.0 g of 1-Methoxy-4-methylcyclohexa-1,4-diene. The reaction mixture is allowed to warm up to approx. -35 C. and stirred for 2 hours at this temperature. A solution of 10.18 g of iodine in 20 ml of tetrahydrofuran and 2.3 ml of acetic acid is then added drop-wise to the reaction mixture and the temperature was allowed to warm up to 0 C. The mixture was stirred for 1 hour at 0 C. and 16 hours at 25 C. Then 3.4 g of iodine is added to the reaction mixture and stirring is continued for additional 24 hours at 25 C. The reaction is finally quenched by pouring the reaction mixture onto a mixture of 250 ml of aeq. Sodium bisulfite (38-40%) and 400 ml of saturated aeq. sodium carbonate. The aqueous phase is extracted with ethyl acetate (1*200 ml and 2*100 ml), the ethyl acetate phases are unified and washed with 100 ml of water. The organic phase was dried over anhydrous sodium sulfate and evaporated in vacuo to give a yellow viscous liquid. The liquid was dissolved in hexane/t-butyl-methylether and the solution was filtered over silica gel to obtain, after evaporation of the solvent, 4.33 g of crude product. The product can be used directly in the next step. Alternatively, it can be purified e.g. by column chromatography on silica gel with hexane/t-butyl-methylether (9:1) as eluent to yield pure N-(2-Chloro-6′-fluoro-phenyl)-4-methylaniline. 1H-NMR (DMSO-d6, 500 MS, 300K) delta 2.17 (s, 3H, CH3); 6.53 [dd, J=8.5 Hz, JH-F=1.5 Hz, 2H, HC (2) and HC (6)], 6.94 [d, J=8.0 Hz, 2H HC (3) and HC (5)], 7.16 [ddd, J=8.0 Hz, JH-F=6.0 Hz, 1H, HC (4′)], 7.25 [ddd, J=8.0, 1.5 Hz, JH-F=8.0, 1H, HC (5′)]; 7.34 [ddd, J=8.0, 1.5 Hz, JH-F, 1.5, 1H, HC (3′)]; 7.63 (s, 1H, NH). MS (EI) m/z 235 (100, M+), 200 (35, (M-Cl)+), 185 (55)

The synthetic route of 2-Chloro-6-fluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Acemoglu, Murat; Allmendinger, Thomas; Calienni, John Vincent; Cercus, Jacques; Loiseleur, Olivier; Sedelmeier, Gottfried; Xu, David; US2008/249318; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 363-51-9, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 363-51-9 as follows.

EXAMPLE 7 (1H-Benzimidazol-2-yl)-(2-chloro-6-fluorophenyl)amine hydrochloride 2-Chloro-6-fluoroaniline (0.48 g) and 2-chlorobenzimidazole (0.5 g) were mixed in a flask and then kept at 170 C. for 30 min. After cooling, the residue was dissolved out of the flask at boiling heat using 1 N HCl and 10% ethanol. The material dissolved out was then stirred at RT for 30 min, then the insoluble material was filtered off with suction and the filtrate was evaporated. The residue was purified by means of preparative HPLC on RP-18 using acetonitrile/water (0.05% TFA). The clean fractions were combined, the acetonitrile was stripped off, the residue was adjusted to pH 10 with potassium carbonate solution, extracted three times with EA, and then the combined phases were dried, filtered, and concentrated. The residue was taken up using HCl/water and freeze-dried. 27 mg of the title compound were obtained. LCMS-Rt: 3.45 min; MS (ES+, M+H+): 262.0

According to the analysis of related databases, 363-51-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hofmeister, Armin; Heinelt, Uwe; Lang, Hans-Jochen; Bleich, Markus; Wirth, Klaus; Gekle, Michael; US2002/132842; (2002); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 363-51-9, name is 2-Chloro-6-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 363-51-9

To the solution of H(3-(trifiuoFomethyl phenyf)sulfonyl)indolirte-6-carboxyiic acid (50 mg, 0.13 mmol): in 1 mi of anhydrous THF at 0 C were added oxayl chloride (23 pL, 0.27 mmol) and a drop of DMF. The reaction was stirred at room temperature for l b. The completion of the reaction was monitored by HPLC, Upon completion, the solvent was removed in vacuo. To the crude residue was added 1 mL of anhydrous THF and 2~chloro-6-fiuoroaniline (78 mg, 0.54 mmol). The reaction was stirred at 55 C for 2h. The completion of the reaction was monitored by HPLC. Upon completion, the solvent was removed in vacuo. The crude product was purified by preparative HPLC (20-100% CH3CN/MeOH (1 :1 ) in H20 (0.01% TFA)) which provided after lyophilization 40 mg (60%) of the title compound as a colorless -solid; 1H NMR (400 MHz, CDCi3) 6 – 8 14 (d, J = 1.3 Hz, 1 H), 8.12 (s, 1 H), 8.02 {d, J – 7.8 Hz, 1 H), 7.85 (d, J ~ 7.1 Hz, 1 H), 7.67 – 7.61 (m, 2 H), 7.59 (s, 1 H), 7.32 – 7,21 (m, 3 H), 7.18 – 7.10 (m, 1 H), 4.02 (1, J – 8,5 Hz, 2 H), 3.03 (1, J = 8.5 Hz, 2 H). MS (Epsilon5Gamma) m/z; 499,02 [M+H+]

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 363-51-9.

Reference:
Patent; THE SCRIPPS RESEARCH INTITUTE; GRIFFIN, Patrick, R.; KAMENECKA, Theodore, M.; DOEBELIN, Christelle; CHANG, Mi, Ra; (109 pag.)WO2018/52903; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 363-51-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 363-51-9, name is 2-Chloro-6-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a 0 C stirred solution of 5-fluoro-4-(3-oxo-5,6 -dihydro-3H-[1 ,2,4]triazolo[3,4-c][1 ,4]oxazin- 2(8H)-yl)-2-{[(2S)-1 ,1 ,1 -trifluoropropan-2-yl]oxy}benzoic acid (intermediate 24) (74.3 mg, 190 muiotaetaomicronIota) and DMF (3 drops) in anhydrous dichloromethane (0.95 ml) was added oxalyl chloride dropwise (28,9 mg, 0.23 mmol). The resulting mixture was warmed to room temperature, stirred for one hour and concentrated under reduced pressure. A solution of the crude acid chloride in dichloromethane (0.63 ml) was then added dropwise to a 0 C stirred solution of 2- chloro-6-fluoraniline (30.4 mg, 0.21 mmol) and triethylamine (21 .1 mg, 0.21 mmol) in dichloromethane (0.70 ml). Following complete addition, the mixture was warmed to room temperature and stirred for one hour. Aqueous hydrochloric acid (1 .0 M, 10 ml) was added to the residue and extracted with dichloromethane (3 x 10 ml). The combined organic extracts were washed with brine (10 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a pale yellow oil. The residue was purified by reverse phase column chromatography (acetonitrile, 0.1 % aqueous formic acid) to give the amide as a white solid (73.3 mg, 66 %).LC-MS (method A): Rt = 1 .18 min; MS (ESIpos): m/z = 519 [M+H]+1H-NMR (400 MHz, CHLOROFORM-d) delta [ppm]: 1 .572 (8.35), 1 .659 (7.01 ), 1.676 (7.05), 3.807 (2.84), 3.820 (4.22), 3.834 (3.51 ), 4.086 (3.74), 4.098 (3.02), 4.100 (4.34), 4.1 13 (2.89), 4.772 (16.00), 4.91 1 (0.46), 4.927 (1 .09), 4.942 (1 .41 ), 4.958 (1 .09), 4.973 (0.42), 7.1 12 (0.89), 7.1 16 (0.94), 7.133 (1 .48), 7.136 (1 .96), 7.140 (1 .10), 7.155 (1.20), 7.159 (1 .25), 7.222 (0.85), 7.235 (0.84), 7.242 (1 .98), 7.256 (2.1 1 ), 7.263 (2.04), 7.285 (2.13), 7.290 (2.75), 7.305 (0.88), 7.309 (1 .07), 7.312 (0.89), 7.463 (2.95), 7.477 (2.96), 8.182 (3.04), 8.212 (3.06), 9.021 (2.04).

The synthetic route of 2-Chloro-6-fluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; THE BROAD INSTITUTE, INC.; PRESIDENT AND FELLOWS OF HARVARD COLLEGE; THE GENERAL HOSPITAL CORPORATION; GRADL, Stefan, Nikolaus; NGUYEN, Duy; EIS, Knut; GUENTHER, Judith; STELLFELD, Timo; JANZER, Andreas; CHRISTIAN, Sven; MUELLER, Thomas; EL SHEIKH, Sherif; ZHOU, Han, Jie; ZHAO, Changjia; SYKES, David B; FERRARA, Steven, James; LIU, Kery; HERBERT, Simon, Anthony; MERZ, Claudia; NIEHUES, Michael; NISING, Carl, Friedrich; SCHAeFER, Martina; ZIMMERMANN, Katja; KNAEBLEIN, Joerg; THEDE, Kai; FAUPEL, Thomas; (539 pag.)WO2018/77944; (2018); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics