Category: 2106-04-9

Application of 2106-04-9, A common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.

Toluene (250 g) and water (150 g) were added to 50.0 g (0.34 mol) of 3-chloro-4-fluoroaniline and the mixture was heated to 60 C. Into this reaction mixture was added dropwise 50.7 g (0.36 mol) of benzoyl chloride. At the same time, a 10% aqueous sodium hydroxide solution was added dropwise thereto to maintain the pH around 8. After the dropwise addition was completed, the mixture was stirred for 2 hours and cooled in ice. The precipitate was filtered, washed with water, and dried to obtain 74.8 g of the title compound (yield: 87%) as a white solid. 1H-NMR (CDCl3, deltappm) 7.11-7.18 (2H, m), 7.50-7.61 (3H, m), 7.88-7.90 (2H, m), 8.05 (1H, brs), 8.38-8.42 (1H, m).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; MITSUI CHEMICALS AGRO, INC.; Kitajima, Kazuki; Kodaka, Kenji; Katsuta, Hiroyuki; Okumura, Kunio; US2013/317247; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 2106-04-9, name is 3-Chloro-2-fluoroaniline, A new synthetic method of this compound is introduced below., Recommanded Product: 2106-04-9

Step A3: 2-[(3-Chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-Pyrrole-3-carboxylic acid ethyl ester Methanesulfonyl chloride (10.62 mmol) was added to a mixture of 2-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester (Step A4) (4.09 mmol), pyridine (14.01 mmol) and DMAP (1.226 mmol) in CH2Cl2 (70 mL). After stirring for 20 h, the reaction mixture was diluted with CH2Cl2 and washed with a saturated aqueous solution of NH4Cl (2*). The combined aqueous phases were back-extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered and concentrated. A mixture of the crude intermediate and 3-chloro-2-fluoro-phenylamine [2106-04-9] (11.64 mmol) in dioxane (90 mL) was stirred at 90 C. for 11 h. After cooling to rt, the reaction mixture was diluted with EtOAc and successively washed with 10% w/w aqueous citric acid and brine. The combined aqueous phases were back-extracted with EtOAc. The combined organic phases were dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep silica gel column to afford the title compound as a yellow solid. tR: 9.08 min (HPLC 2); ESI-MS: tR=1.54 min, [M]+318/320 (i.e. fragmented pyrrolium ion) (LC-MS 1); TLC: Rf=0.45 (1:4 EtOAc/hexanes).

The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; Cotesta, Simona; Furet, Pascal; Guagnano, Vito; Holzer, Philipp; Kallen, Joerg; Mah, Robert; Masuya, Keiichi; Schlapbach, Achim; Stutz, Stefan; Vaupel, Andrea; US2013/317024; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-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. category: chlorides-buliding-blocks

To 3-chloro-2-fluoroaniline (10.0 g, 68.7 mmol) in DMSO (500 mL) was added copper (II) chloride (18.5 g, 137.4 mmol) and conc. HCl (50 mL). The whole was heated to 90 C. for 13 h. The reaction was cooled to 0 C. and 4N NaOH was added dropwise to adjust to pH 8. The reaction was diluted with water and extracted with Et2O/EtOAc (1:1). The organic layer was washed with brine, and was dried, filtered and concentrated. The resulting residue was purified via silica gel chromatography eluding with 5-30% EtOAc/hexane to provide 4-amino-2-chloro-3-fluoro-benzaldehyde (1.00 g) as a yellow powder.

The synthetic route of 3-Chloro-2-fluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nirschl, Alexandra; Sutton, James C.; Hamann, Lawrence; Wang, Tammy; Zou, Yan; Sun, Chongqing; US2005/197359; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 2106-04-9, A common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.

Step 1: 5-Bromo-N-(3-chloro-2-fluorophenyl)pyridin-3-amineA 20 mL microwave vial was charged with 3-chloro-2-fluoroaniline (473 jiL, 4.22 mmol) and diluted with 1,4-dioxane (16.9 mL). To that solution was added 3,5- dibromopyridine (1000 mg, 4.22 mmol), sodium tert-butoxide (568 mg, 5.91 mmol),xantphos (48.9 mg, 0.0840 mmol), and tris(dibenzylideneacetone)dipalladium(0) (38.7 mg, 0.0420 mmol). The vial was sealed and degassed using ultra pure argon and sonication for 1 mm. The vial was placed into a reaction block preheated to 80 C. After 1 h, the contents of the vial were transferred to a flask, and the volatiles were concentrated under reduced pressure. The resulting brown solids were dissolved with ethyl acetate andwater. The contents of the flask were transferred into a separatory funnel where the layers were separated. The organic was washed with water and brine, dried over magnesium sulfate, and purified by silica gel flash chromatography. Upon dissolving the sample with DCM, a white solid persisted, which was collected by filtration and washed with hexanes to give 541 mg of desired product. The supernatant was concentrated under reducedpressure and purified by silica gel column chromatography (24 g ISCO RediSep Rf, loaded inlwith: DCM and dried, initial waste: 0 mL, fraction size: 9 mL 13x 100 mm, and eluted with ethyl acetate in dichloromethane 0% [75 mL], 0-5% [201 mL], 5% [300 mL]).The fractions were collected and combined with the previously collected solids to give 921 mg(72%). ?H NMR (400MHz, CDC13)oe 8.35 (d,J=2.5 Hz, 1H), 8.31 (d,J1.8 Hz, 1H), 7.58 (t,J=2.1 Hz, 1H), 7.22-7.14 (m, 1H), 7.08-7.01 (m, 2H), 5.86 (br. s., 1H). Mass found 302 [M+H] .

The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; DELUCCA, George V.; GAVAI, Ashvinikumar V.; QUESNELLE, Claude A.; GILL, Patrice; O’MALLEY, Daniel; VACCARO, Wayne; LEE, Francis Y.; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; FANG, Haiquan; HILL, Matthew D.; HUANG, Hong; SCHMITZ, William D.; STARRETT, JR, John E.; HAN, Wen-Ching; TOKARSKI, John S.; MANDAL, Sunil Kumar; WO2015/100282; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 2106-04-9, 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. 2106-04-9 name is 3-Chloro-2-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.

EXAMPLE 3; Step 1 A round bottom flask was charged with 1 eq of 3-chloro-2-fluoroaniline (3A), 1-methyl-2-pyrrolidinone (about 1.5 M 3A in NMP), 2.2 eq of sodium cyanide, and 1.35 eq of nickel(II) bromide at RT under N2. The concentration was halved by the introduction of additional NMP under N2 and the solution was gently warmed to 200+/-5 C. and stirred for 4 days under N2. The reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with 30 volumes of tert-butyl methyl ether (MTBE) and filtered through celite. The celite pad was then rinsed with 10 volumes of MTBE. The organics were washed with 40 volumes of brine, 2¡Á40 volumes of water and 40 volumes of brine. The combined organics were dried over sodium sulfate and concentrated to afford a brown solid, which was dried under vacuum (30 in Hg) at 40 C. for 8 hours to afford the compound of Formula 3B (71% yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Chloro-2-fluoroaniline, and friends who are interested can also refer to it.

Reference:
Patent; Muci, Alex; Lu, Pu-Ping; Morgan, Bradley P.; Morgans, JR., David J.; US2009/192168; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-04-9, These common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-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.

Example 1; 4- (3-CHLORO-2-FLUOROANILINO)-6- [1- (HYDROXYACETYL) PIPERIDIN-4-YLOXY]-7- methoxyquinazoline; HATU (28.9 g) was added to a stirred solution of 4- (3-chloro-2-fluoroanilino)-7- METHOXY-6- (PIPERIDIN-4-YLOXY) quinazoline dihydrochloride (30 g), glycolic acid (5.40 g) and di-isopropylethylamine (44.70 ml) in methylene chloride (900 ml). After 1.5 hours the reaction mixture was washed with sodium hydroxide solution (2M), water and saturated brine. The resulting product was then purified by flash chromatography on silica eluting with 3% MeOH/methylene chloride. The fractions containing the desired product were combined and reduced in vacuo to give the title product as a white solid which was recrystallised from acetonitrile (29.6 g); NMR Spectrum : (DMSO d6) 1.65-1. 81 (m, 2H), 1.99-2. 10 (m, 2H), 3.26- 3.34 (m, 1H), 3.37-3. 47 (m, 1H), 3.60-3. 68 (m, 1H), 3.81-3. 89 (m, 1H), 3.95 (s, 3H), 4.14 (d, 2H), 4.50 (t, 1H), 4.78 (m, 1H), 7.25 (s, 1H), 7.30 (t, 1H), 7.46-7. 55 (m, 2H), 7.88 (s, 1H), 8.40 (s, 1H), 9.55 (s, 1H) ; Mass Spectrum: (M+H) + 460.94. THE 4- (3-CHLORO-2-FLUOROANILINO)-7-METHOXY-6- (PIPERIDIN-4-YLOXY) quinazoline dihydrochloride starting material was prepared as follows: 6-Acetoxy-4-chloro-7-methoxyquinazoline, (Example 25-5 in WO01/66099 ; 10. 0G, 39.6 mmole) was added in portions to a stirred 7N methanolic ammonia solution (220 ml) cooled to 10C in an ice/water bath. After stirring for one hour the precipitate was filtered, washed with diethylether and dried thoroughly under high vacuum to give 4-chloro-6- hydroxy-7-methoxyquinazoline (5.65 g, 67.8 %); NMR Spectrum: (DMSO d6) 3.96 (s, 3H); 7.25 (s, 1H); 7.31 (s, 1H); 8.68 (s, 1H); Mass Spectrum : (M+H) + 211 Di-tert-butylazodicarboxylate (9.22 g) in methylene chloride (20 ml) was added slowly to a stirred suspension of 4-chloro-6-hydroxy-7-methoxyquinazoline (5.63 g), 4-hydroxy-1- tert-butoxycarbonylpiperidine (8.06 g) and triphenylphosphine (10.5 g) in methylene chloride (100 ml) at 5C under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature for 16 hours. The reaction mixture was then evaporated under vacuum and adsorbed onto silica and the product was eluted with isohexane/ethyl acetate/triethylamine (75/24/1 followed by 70/29/1). The fractions containing the desired product were combined and evaporated under vacuum to give tert-butyl 4- [ (4-CHLORO-7-METHOXYQUINAZOLIN-6- yl) oxy] piperidine-l-carboxylate as a white solid (10.3 g) ; IH NMR SPECTRUM : (DMSO d6) 1.40 (s, 9H), 1.56-1. 69 (m, 2H), 1.93-2. 04 (m, 2H), 3.20-3. 31 (m, 2H), 3.60-3. 70 (m, 2H), 4.00 (s, 3H), 4. 89 (m, 1H), 7.45 (s, 1H), 7.50 (s, 1H), 8.86 (s, 1H) ; Mass Spectrum : (M+H) + 394. 4. 0M HC1 in Dioxane (4.0 ml) was added to a suspension of tert-butyl 4- [ (4-chloro-7- methoxyquinazolin-6-yl) oxy] PIPERIDINE-1-CARBOXYLATE (2.62 g) and 3-chloro-2-fluoroaniline (1.08 g) in iso-propanol (50 ml). The reaction mixture was stirred and heated at 100C for 2 hours. The yellow precipitate was filtered hot and washed with iso-propanol followed by diethylether and dried under vacuum to give 6- (PIPERIDIN-4-YLOXY)-4- (3-CHLORO-2- fluoroanilino) -7-methoxyquinazoline as a di-hydrochloride salt (2.38 g) ; 1H NMR SPECTRUM (DMSO D6) 1.84-1. 99 (m, 2H), 2.22-2. 33 (m, 2H), 3.12-3. 33 (m, 4H), 4.00 (s, 3H), 5. 08 (m, 1H), 7.34 (t, 1H), 7.40 (s, 1H), 7.50 (t, 1H), 7.62 (t, 1H), 8.80 (s, 1H), 8. 84-8. 94 (m, 2H), 8.99-9. 11 (m, 1H); Mass Spectrum: (M+H) + 403.

The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/12290; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 2106-04-9, name is 3-Chloro-2-fluoroaniline, A new synthetic method of this compound is introduced below., name: 3-Chloro-2-fluoroaniline

4. 0M HC1 in Dioxane (4.0 ml) was added to a suspension of tert-butyl 4- [ (4-chloro-7- methoxyquinazolin-6-yl) oxy] piperidine-1-carboxylate (2.62 g) and 3-chloro-2-fluoroaniline (1.08 g) in iso-propanol (50 ml). The reaction mixture was stirred and heated at 100C for 2 hours. The yellow precipitate was filtered hot and washed with iso-propanol followed by diethylether and dried under vacuum to give 6- (piperidin-4-yloxy)-4- (3-chloro-2- fluoroanilino)-7-methoxyquinazoline as a di-hydrochloride salt (2.38g) ; 1H NMR Spectrum : (DMSO d6) 1.84-1. 99 (m, 2H), 2.22-2. 33 (m, 2H), 3.12-3. 33 (m, 4H), 4.00 (s, 3H), 5.08 (m, 1H), 7.34 (t, 1H), 7.40 (s, 1H), 7.50 (t, 1H), 7.62 (t, 1H), 8.80 (s, 1H), 8. 84-8. 94 (m, 2H), 8. 99-9.11 (m, 1H) ; Mass Spectrum: (M+H) + 403.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2003/82831; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 2106-04-9, A common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.

a 2-Fluoro-3-chlorophenylisothiocyanate Into a solution of 2-fluoro-3-chloroaniline (1.0 g, 6.87 mmol) in 30 mL of toluene at room temperature, thiophosgene (0.8 mL, 10.3 mmol) and triethylamine (1.12 mL, 8.24 mmol) were added. The mixture was stirred at room temperature for 16 hours. The mixture was parationed between ethyl acetate and water. The combined organic layer was then concentrated to give the desired product (950 mg, 74%). 1H NMR (CDCl,) delta 7.09 (m, 2H), 7.30 (m, 1H).

The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Palovich, Michael R.; Widdowson, Katherine L.; Nie, Hong; US2003/216375; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 2106-04-9, These common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-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.

A suspension of compound 5 (1.70 g, 6.75 mmol) and 3-chloro-2-fluoroaniline (982 mg, 6.75 mmol) in i-PrOH (50 mL) was heated to reflux for 3 h. The solvent was removed under vacuum, and the residual was recrystallized in CH3CN to afford 6 (2.51 g, 93%) as a pale brown solid, mp 209-210 C. 1H NMR (DMSO-d6): d 9.82 (br s, 1H), 8.48 (s, 1H), 8.23 (s, 1H), 7.53-7.47 (m, 2H), 7.37 (s, 1H), 7.28 (t, J = 8.0 Hz, 1H), 3.96 (s, 3H), 2.37 (s, 3H). LC-MS (ESI, m/z): calcd for C17H14ClFN3O3 ([M+H]+) 362.0, found 362.0.

The synthetic route of 2106-04-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang; Bioorganic and Medicinal Chemistry Letters; vol. 24; 18; (2014); p. 4455 – 4459;,
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. 2106-04-9, name is 3-Chloro-2-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H5ClFN

Step 7. Preparation of compound (I). 2-[4-(5-cyano-4-{ [(dimethylamino)methylene] amino } -2-methoxyphenoxy)piperidin- 1 -yl] -JV-methylacetamide (compound (II),; 7.00 g, 17.71 mmoles), was suspended in methoxybenzene (35.8 g). Acetic acid (16.6 g) was charged and to the resulting solution was added 3-chloro-2-fluoroaniline (2.71 g, 18.07 mmoles). The reaction mixture was heated at 90 0C for 20 hours then cooled to 200C. Water (37.04 g) was charged to the reaction mixture, and the organic layer discarded. To the resulting aqueous mixture was charged isopropanol (39.00 g), followed by aqueous ammonia (20.79 g, 25%). The reaction mixture was heated to 30 0C and seeded with compound (I), which induced crystallisation. The reaction was then cooled to 00C and the product isolated by filtration. The filter cake was washed twice with a mixture of water (7.28 g) and isopropanol (4.68 g), then dried to afford the compound (I) (5.65 g, 55% yield); 1H NMR (400 MHz, DMSO-J6) delta ppm 1.79 (m, 2 H) 2.04 (m, 2 H) 2.38 (m, 2 H) 2.62 (d, J=4.5 Hz, 3 H) 2.74 (m, 2 H) 2.94 (s, 2 H) 3.93 (s, 3 H) 4.56 (tt, J=8.1, 3.8 Hz, 1 H) 7.21 (s, 1 H) 7.28 (m, 1 H) 7.50 (m, 2 H) 7.73 (q, J=4.5 Hz, 1 H) 7.81 (s, 1 H) 8.36 (s, 1 H) 9.56 (br.s, 1 H); Mass Spectrum: m/z (M + H)+ 474.2, 476.2.

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 2106-04-9.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BOARDMAN, Kay, Alison; CUNNINGHAM, Oliver, Robert; GOUNDRY, William; LAFFAN, David, Dermot, Patrick; WO2010/122340; (2010); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics