Month: December 2020

Adding a certain compound to certain chemical reactions, such as: 54932-72-8, name is 4-Bromo-1-chloro-2-methylbenzene, belongs to chlorides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 54932-72-8, 54932-72-8

General procedure: Nitrogen was purged through a stirred solution of 4-bromo-1-chloro-2-methylbenzene (258muL, 1.95mmol) in 1,4-dioxane (5mL) for 30min rac-BINAP (363mg, 1.95mmol), caesium carbonate (1.27g, 3.89mmol), 1-Boc-piperazine (363mg, 1.95mmol) and Pd(OAc)2 (87mg, 0.039mumol) and stirred at reflux for 14h under N2. The reaction was filtered through celite and concentrated in vacuo. The residue was dissolved in EtOAc (20mL), filtered through celite and washed with additional EtOAc (50mL). The organic layer was washed with water (2¡Á20mL) and brine (2¡Á20mL), dried with Na2SO4 and concentrated in vacuo. The crude residue was purified by column chromatography (100% CyHex to 10% EtOAc/CyHex) to obtain the protected intermediate as a solid (413mg, 68%). MS, m/z=255 (100) [M-tBu]. The intermediate was dissolved in a 1:3 mixture of TFA/DCM (4mL) and stirred at 20C for 1h. The solvent was evaporated in vacuo and the crude residue dissolved in EtOAc (10mL) which was successively washed with a 10% solution of NaHCO3 (10mL), water (10mL) and brine (10mL). The organic layer dried with Na2SO4 and concentrated in vacuo to obtain 92 as a solid (211mg, 76%).

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, 4-Bromo-1-chloro-2-methylbenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Blackmore, Timothy R.; Jacobson, Jonathan; Jarman, Kate E.; Lewin, Sharon R.; Nguyen, William; Purcell, Damian F.; Sabroux, Helene Jousset; Sleebs, Brad E.; European Journal of Medicinal Chemistry; vol. 195; (2020);,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

112-26-5, 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. 112-26-5 name is 1,2-Bis(2-chloroethoxy)ethane, 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.

A 50 mL round-bottomed flask was sequentially charged with 8 mmol of N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-(piperazin-1-yl). Base) benzamide compound 1, 30 mmol 1,2-bis(2-chloroethoxy)ethane, 10 mmol anhydrous potassium carbonate, and 20 mL N,N-dimethylformamide (DMF). The reaction was stirred overnight at 60 degrees Celsius, extracted with ethyl acetate and dried over anhydrous sodium sulfate.The solvent was removed on a rotary evaporator and the residue was chromatographed on a silica gel column to give the product 4-((4-(2-(2-(2-chloroethoxy)ethoxy)ethyl)piperazin-1-yl)methyl. (amino)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide compound m (yield: 72%)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,2-Bis(2-chloroethoxy)ethane, and friends who are interested can also refer to it.

Reference:
Patent; Hefei Zhong Popular Science Ruisheng Bio-pharmaceutical Technology Co., Ltd.; Liu Qingsong; Liu Jing; Wang Qiang; Liu Feiyang; Wang Beilei; Wang Aoli; Wang Wenchao; Hu Chen; Chen Cheng; Zhao Zheng; Wu Hong; Wang Li; (52 pag.)CN104844566; (2018); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

6940-78-9, Name is 1-Bromo-4-chlorobutane, 6940-78-9, 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.

50 g of 7-hydroxy-1H-quinolin-2-one and 400 mL of ethanol and 62.7 g of triethylamine were charged into a 1 L three-necked reaction flask and heated to 60 C,Then 159.5 g of 1-bromo-4-chlorobutane was added dropwise,The temperature was raised to 80 C and the reaction was kept at reflux for 2 hours.The reaction was stopped,Cooled to 10 C,Stirred for 1 hour,The crude product was collected by filtration and then recrystallized from 500 ml of methanol. After heating to reflux, the mixture was cooled to room temperature, stirred for 1 hour, filtered, rinsed with cold methanol 50 mL and dried at 60 C under normal pressure to give 72.0 g. G, yield: 92.2%, HPLC purity 99.5% (1: 2.0)

Statistics shows that 1-Bromo-4-chlorobutane is playing an increasingly important role. we look forward to future research findings about 6940-78-9.

Reference:
Patent; SHANDONG CHUANGCHENG PHARMACEUTICAL CO., LTD; Guo, Ming; Ma, Juliang; Liu, Huaizhen; (6 pag.)CN106008337; (2016); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

933190-51-3, 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 933190-51-3 as follows.

A microwave vial was charged with a mixture of 8-bromo-6- chloroimidazo[l,2-b]pyridazine (0.8 g, 3.44 mmol), isoquinolin-4-ylboronic acid (0.6 g, 1.734 mmol), dioxane (16 mL), tetrakis(triphenylphosphine)palladium(0) (0.100 g, 0.087 mmol), and K3PO4 (2.60 mL, 5.20 mmol) (2.0 M water solution) was stirred at room temperature for 5 min. under nitrogen. The resulting mixture was heated to 100 C for 4 h in microwave. The reaction mixture was cooled to room temperature, quenched with water, and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3 X 20 mL). The combined organic layer was washed with brine, dried over anhydrous Na2S04, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by BIOTAGE (30-100% EtOAc/ EtOAc/CH2Cl2, 1.2 L, then 50-100%B/ EtOAc/CH2Cl2, B: 10% MeOH/EtOAc/CH2Cl2, 800 mL) to give the product (0.27 g, 55%). XH NMR (400 MHz, CDC13) delta ppm 9.41 (1 H, s), 8.72 (1 H, s), 8.66 (1 H, d, J=4.53 Hz), 8.03-8.17 (1 H, m), 7.90 (1 H, s), 7.71 (3 H, d, J=3.02 Hz), 7.26 (1 H, d, J=4.53 Hz); LC/MS: Rt = 1.35 min. LC/MS (Condition A): 281.13/283.13.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 933190-51-3, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; LIU, Peiying; BALOG, James Aaron; WO2011/137155; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, I believe this compound will play a more active role in future production and life. 1996-29-8

In a sealed tube, to a stirred solution of ferf-butyl (3-(2-oxoimidazolidin-1 – yl)bicyclo[1 .1 .1 ]pentan-1 -yl)carbamate (0.25 g, 0.935 mmol, 1 .0 equiv.) in 1 , 4-dioxane (5 mL) was added 1 -bromo-4-chloro-2-fluorobenzene (0.19 g, 0.935 mmol, 1 .0 equiv). The mixture was degassed by purging with argon for 5 minutes. Then Pd2(dba)3 (0.085 g, 0.093 mmol, 0.1 equiv), xanthphos (0.1 g, 0.187 mmol, 0.2 equiv) and Cs2C03 (1 .21 g, 3.74 mmol, 4.0 equiv) were added to the reaction mixture under argon atmosphere, and the sealed tube was capped and the mixture was stirred at 80 C for 16 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (20 mL), filtered through a Celite bed, and the Celite bed washed with excess ethyl acetate. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by silica gel column chromatography (Combiflash) using 50 % Ethyl acetate in hexane as eluent to obtain ferf-butyl 3-(3-(4-chloro-2-fluorophenyl)-2-oxoimidazolidin-1 – yl)bicyclo[1 .1 .1 ]pentan-1 -yl)carbamate (0.17 g, 65% yield) as an off-white solid. LCMS (ES) m/z = 396.1 [M+H] +.

The chemical industry reduces the impact on the environment during synthesis 1996-29-8. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; AXTEN, Jeffrey Michael; DEMARTINO, Michael P.; EVANS, Karen Anderson; RALPH, Jeffrey M; KALITA, Biswajit; (278 pag.)WO2018/225093; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2770-11-8,Some common heterocyclic compound, 2770-11-8, name is 2-(4-Chlorophenoxy)aniline, molecular formula is C12H10ClNO, 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.

To a magnetically stirred solution of 2-(4-chlorophenoxy)aniline (95 mg, 0.432 mmol, 76 muL) in CH2Cl2 (1.5 mL) at room temperature was added dropwise propionylchloride (48 mg, 0.518 mmol, 45 muL) followed several minutes later by ethyldiisopropylamine (0.2 mL). The reaction was stirred at room temperature for a further 17 hours, quenched with H2O (10 mL) and partitioned with CH2Cl2 (10 mL). The aqueous layer was extracted with CH2Cl2 (10 mL), and the combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified over silica gel with 0-50% ethyl acetate in cyclohexane to yield N-[2-(4-chlorophenoxy)phenyl]propanamide (109 mg, 0.395 mmol), Example 14, in 91% yield. LCMS ESI+: 276 [M+H]+, Rt 9.1 min (LCMS 01).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(4-Chlorophenoxy)aniline, its application will become more common.

Reference:
Patent; Bioversys AG; Schneider, Peter; Riedl, Rainer; Tigges, Marcel; Gitzinger, Marc; Pieren, Michel; Levi, Assaf; Sephton, Mark; Schellhorn, Birgit; Zueger, Patrik; Brand, Michael; Gygax, Daniel; Spies, Peter; EP2762134; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

626-43-7, 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 626-43-7 as follows.

Under constant stirring at 0 C, to a solution of 3,5-dichloroaniline (3.24 g, 20 mmol)concentrated hydrochloric acid solution (12 mL)35 wt.% aqueous solution of acetaldehyde (12.8 mL, 80 mmol) was added dropwise. The reaction mixture was stirred at 0 C for 15 minutes and then gradually warmed to 75 C. And reacted at this temperature for 4 hours. The reaction was cooled to room temperature, poured into ice water, 25% aqueous ammonia solution was added dropwise and made alkaline,Extract with dichloromethane three times.The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure.The crude product was isolated and purified by silica gel column chromatography (ethyl acetate / petroleum ether, 1: 20) to obtain 2.93 g of the compound 1 as a pale yellow solid in a yield of 69%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 626-43-7, and friends who are interested can also refer to it.

Reference:
Patent; Guangdong University of Technology; Centre national de la recherche scientifique (CNRS); LIU, YAN; LIU, XING GUO; HUANG, DA YA; HUANG, MEI JIE; WANG, DE AN; NGUYEN, MICHELLE; ROBERT, ANNIE; MOONEY, BERNARD; (18 pag.)CN105949120; (2016); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 6775-78-6, name is 6-Chloroimidazo[1,2-b]pyridazine, molecular formula is C6H4ClN3, 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. 6775-78-6

b) 3-Bromo-6-chloroimidazo[1 ,2-b]pyridazine; Bromine (3.8 mL, 74.19 mmol) was added dropwise to a solution of 6-chloroimidazo [1 ,2-b]pyridazine (Preparation 1 a, 4.8 g, 31.06 mmol) in glacial acetic acid (80 mL) and the resulting mixture was stirred at ambient temperature for 20 minutes. The precipitate formed was collected by filtration, washed with diethyl ether several times and dried in vacuo. The solid obtained was partitioned between ethyl acetate and a saturated aqueous solution of potassium carbonate. The organic layer was separated and washed with a saturated aqueous solution of potassium carbonate, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude was then treated with pentane, filtered and the solid obtained was dried in vacuo to yield the title compound (6.6 g, 92%) as a pale yellow solid.LRMS (m/z): 232 (M+1)+.1H-NMR delta (300 MHz, CDCI3):7.13 (d, 1H), 7.80 (s, 1H), 7.92 (d, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6775-78-6, its application will become more common.

Reference:
Patent; ALMIRALL,S.A.; GONZALEZ RODRIGUEZ, Jacob; VIDAL JUAN, Bernat; VIDAL GISPERT, Laura; BACH TANA Jordi; WO2012/69202; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

108-37-2, These common heterocyclic compound, 108-37-2, name is 1-Bromo-3-chlorobenzene, 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.

Under a nitrogen atmosphere, a 5 L dry and clean four-neck round bottom flask was charged with diisopropylamine (72.8 g, 0.72 mol, 1.06 eq) and 1500 mL of anhydrous tetrahydrofuran, and the temperature was reduced to -70 C.Add n-butyllithium solution (272mL, 2.5M, 0.68mol, 1.0eq), stir to cool to -70 , slowly add D-1 (130g, 0.68mol, 1.0eq) dropwise, and maintain the reaction for 1h after the addition.Slowly add iodine-tetrahydrofuran solution (172g iodine / 300ml THF, 0.68mol, 1.0eq),After the addition, the reaction was maintained for 1 h.The temperature was slowly raised to room temperature, and the reaction was monitored by HPLC for completion.The reaction was quenched with 500 mL of 5% Na2S2O3 solution, and extracted with 2 L of methyl tert-butyl ether.The organic phase was washed with 1500 mL of saturated saline and dried over anhydrous sodium sulfate.Concentrated under reduced pressure to obtain an oil, and recrystallized by adding 600 mL of ethanol.184 g (F-1) of white flaky solid was obtained by filtration,The yield was 85%.

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 108-37-2.

Reference:
Patent; Ningbo Lumilan New Materials Co., Ltd.; Ningbo Dinghao Optoelectric Materials Technology Co., Ltd.; Zhang Yuxiang; Zhang Qingyun; Ding Huanda; Chen Zhikuan; (41 pag.)CN110551154; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

6775-78-6, A common heterocyclic compound, 6775-78-6, name is 6-Chloroimidazo[1,2-b]pyridazine, molecular formula is C6H4ClN3, 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.

478 mg (3.11 mmol) of 6-chloroimidazo[1 ,2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N- bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with saturated sodium chloride solution and dried over sodium sulfate. Sn the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions. 1H-NMR (CHLOROFORM-d): delta [ppm] – 7.12 (d, 1 H); 7.79 (s, 1 H); 7.90, (d, 1 H).

The synthetic route of 6775-78-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; EIS, Knut; WO2013/87581; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics