Category: chlorides-buliding-blocks

445-14-7,Some common heterocyclic compound, 445-14-7, name is 2-Amino-4-chlorobenzotrifluoride, molecular formula is C7H5ClF3N, 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 5 3-((5-chloro-2-(trifluoromethyl)phenyl)ethvnyl)-5-(l-(piperidin-4-yl)-lH-pyrazol-4- yl)-lH-pyrrolor2,3-b1pyridine Step 1) 2-bromo-4-chloro-l-(trifluoromethyl)benzene To a stirred solution of 40percent HBr (2.20 mL, 15.34 mmol) in 0 (2 mL) was added 2-amino-4- chlorobenzotrifluoride (0.50 g, 2.56 mmol) at 0 ¡ãC. Then a solution of sodium nitrite (0.21 g, 3.07 mmol) in H20 (2 mL) was added dropwise at 0 ¡ãC. The mixture was stirred at 0 ¡ãC for a further 0.5 hours, a solution of cuprous bromide (0.63 g, 4.35 mmol) in 40percent HBr (2.20 mL, 15.34 mmol) and H20 (3 mL) was added. The mixture was stirred at 75 ¡ãC for 3 hours, then cooled to rt, and extracted with EtOAc (40 mL x 4). The combined organic phases were washed with brine (80 mL x 2), dried over anhydrous Na2S04 and concentrated in vacuo to give the title compound as a yellow liquid (0.76 g, 100percent). GC -MS: 257.9.

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

Reference:
Patent; CALITOR SCIENCES, LLC; SUNSHINE LAKE PHARMA CO., LTD.; XI, Ning; LI, Xiaobo; ZHOU, Shiqing; WO2014/89280; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

A common heterocyclic compound, 452-73-3, name is 2-Chloro-4-fluoro-1-methylbenzene, molecular formula is C7H6ClF, 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. 452-73-3.

A mixture of 77.6 g (0.54 mol) of 2-chloro-4-fluorotoluene, 95.6 g(0.54 mol) of N-bromosuccinimide, 1 g of benzoyl peroxide, and 1000 ml of carbon tetrachloride were refluxed for 3 h. The resulting mixture was cooled to room temperature and then filtered through a glass frit (G3). The precipitate was additionally washed with 3 x 100 ml of carbon tetrachloride. The combined filtrate was evaporated to dryness. Fractional distillation of the residue gave pure title product, bp 97-99C/10 mm Hg. Yield 106 g (88%).Anal. calc. for C7H5BrClF: C, 37.62 H, 2.26 Found: C, 37.79; H, 2.34.1H NMR (CDCl3): delta 7.41 (dd, J=8.4 Hz, J=6.0 Hz, IH, 6-H), 7.13 (dd, J=8.4 Hz, J=2.6 Hz, IH, 3-H), 6.97 (dt, J=8.4 Hz, J=2.6 Hz, IH, 5-H), 4.55 (s, 2H, CH2).

The synthetic route of 2-Chloro-4-fluoro-1-methylbenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EXXONMOBIL CHEMICAL PATENTS INC.; WO2007/70041; (2007); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

13526-66-4, Adding some certain compound to certain chemical reactions, such as: 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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 13526-66-4.

13.9 g (59.8 mmol) 3-bromo-6-chloro-imidazo[1 ,2-b]pyridazine were suspended in 508 mL 1 ,4-dioxane. 10.1 g (62.8 mmol) 2-benzofuranylboronic acid, 2.76 g (2.29 mmol) tetrakis(triphenylphosphino)palladium-(0) and 19.0 g (179 mmol) sodium carbonate were added. The obtained mixture was heated to 100C for 24 h. 400 mL of a saturated aqueous ammonium chloride solution were added. The obtained mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the obtained solid material was digested in 40 mL of a mixture of dichloromethane and methanol (8:2), filtered off and dried in vacuo to yield 5.42 g (44%) of the title compound as solid material. 1H-NMR (300 MHz, DMSO-d6): delta [ppm]= 7.23 – 7.40 (m, 2H), 7.51 (d, 1 H), 7.59 – 7.67 (m, 2H), 7.77 (d, 1 H), 8.33 – 8.40 (m, 2H). LCMS (Method 1 ): Rt = 1 .35 min; MS (ESIpos) m/z = 270 [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 13526-66-4.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ZORN, Ludwig; EIS, Knut; SCHULZE, Volker; SUeLZLE, Detlev; PUeHLER, Florian; LIENAU, Philip; BOeMER, Ulf; PETERSEN, Kirstin; HAeGEBARTH, Andrea; WO2014/118135; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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 1127-85-1 as follows. 1127-85-1

Reference Example 36 (S)-tert-butyl 1-(2-chloro-5,6,7,8-tetrahydroquinazolin-4-yl)pyrrolidin-3-yl-(methyl)carbamate Diisopropylethylamine (2.7 ml, 15.5 mmol) was added into chloroform (40 ml) solution of 2,4-dichloro-5,6,7,8-tetrahydroquinazoline (1.5 g, 7.39 mmol) prepared in Reference Example 33 and (3S)-(-)-3-(methylamino)-pyrrolidine (0.87 ml, 8.13 mmol), and then they were stirred at 50 C. overnight. Di-tert-butyldicarbonate (1.69 ml, 7.39 mmol) was added thereto, and they were stirred at room temperature overnight. The reaction mixture was diluted in dichloromethane, washed with water, dried with anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=5/1) to give the titled compound (2.3 g) as a colorless oil. 1H NMR (400 MHz, CDCl3) delta 4.74 (s, 1H), 3.80 (m, 2H), 3.67 (m, 1H), 3.54 (m, 1H), 2.82 (s, 3H), 2.71 (m, 4H), 2.04 (m, 2H), 1.85 (m, 2H), 1.71 (m, 1H), 1.59 (m, 1H), 1.48 (s, 9H).

According to the analysis of related databases, 1127-85-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; YUHAN CORPORATION; SIM, Jae Young; CHA, Myung; KIM, Tae Kyun; YOON, Young Ae; KIM, Dong Hoon; (59 pag.)US2016/90374; (2016); 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. 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, A new synthetic method of this compound is introduced below., 1996-30-1

Carbazole (800 mmol, 133.8 g), 2-bromo-4-chloro-1-fluorobenzene (840 mmol 175.9 g), and dimethylformamide (160 ml) were added to a three-necked flask, and the flask was flushed with nitrogen. Sodium hydride (62% paraffin dispersion) (800 mmol, 31.0 g) was added thereto stepwise five or more times, while observing the amount of hydrogen gas generated, and the reaction mixture was slowly heated while observing the amount of hydrogen gas generated. The reaction mixture was then heated under stirring at a temperature of 150 C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with toluene (1 L), and quenched with a small amount of water in a nitrogen atmosphere. The reaction mixture was filtered by using celite and washed three times with water by using a separatory funnel. The reaction mixture was dried by using anhydrous magnesium sulfate, filtered through a silica gel pad, and then, concentrated. The resultant obtained therefrom was recrystallized in a mixed solvent of ethanol_methanol=1:1 to obtain Intermediate 1-3. The amount of Intermediate 1-3 obtained was 156.1 g and the yield of Intermediate 1-3 was 55%.

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; Samsung Electronics Co., Ltd.; INAYAMA, Satoshi; IRISA, Shiro; KORAI, Keisuke; SAKURAI, Rie; ITO, Mitsunori; NUMATA, Masaki; (265 pag.)US2019/214570; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

363-51-9, A common heterocyclic compound, 363-51-9, name is 2-Chloro-6-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.

Example 66A N-(2-chloro-6-fluorophenyl)-4-ethyl-2-(methylthio)pyrimidine-5-carboxamide Example 28B (15 g, 76 mmol) was dissolved in dioxane (300 mL) and sulfurous dichloride (6.62 ml, 91 mmol). N,N-dimethylformamide (3 drops) were added. The reaction mixture was stirred for 60 minutes at ambient temperature then 2-chloro-6-fluoroaniline (13.22 g, 91 mmol) was added. The reaction mixture was then stirred at 100 C. for 16 hours. The flask was then put into an ice bath and the reaction mixture was quenched by careful addition of saturated aqueous sodium bicarbonate (200 mL). After diluting with 200 mL of ethyl acetate, the reaction mixture was poured into a separatory funnel, the aqueous layer was removed and the organic layer was washed with saturated aqueous sodium bicarbonate (1*150 mL), diluted aqueous sodium bicarbonate (10% wt, 1*150 mL), and saturated aqueous brine (1*150 mL), dried over magnesium sulfate, filtered and concentrated. Purification by silica gel flash chromatography (Isco, Redi-Sep column, 5-85% ethyl acetate/hexane, linear gradient) afforded the title compound.

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

Reference:
Patent; AbbVie Inc.; Woods, Keith W.; Mastracchio, Anthony; Lai, Chunqiu; Gandhi, Viraj B.; Penning, Thomas D.; US2013/225589; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 15205-15-9, name is 2-Chloro-6-fluorobenzylamine, I believe this compound will play a more active role in future production and life. 15205-15-9

Step 1: (S) -tert-Butyl (1- (4- ( (2-chloro-6-fluorobenzyl) carbamoyl) -2- (3, 4-dimethoxyphenyl) oxazol-5-yl) ethyl) carbamate[0569]To 15 mL of dichloromethane were added (S) -5- (1- ( (tert-butoxycarbonyl) amino) ethyl) -2- (3, 4-dimethoxyphenyl) oxazole-4-carboxylic acid (0.3 g, 0.764 mmol) , 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (219.65 mg, 1.15 mmol) and 1-hydroxy-7-azabenzotriazole (156.4 mg, 1.15 mmol) . The mixture was stirred at 0 for 30 minutes. To the mixture were added dropwise (2-chloro-6-fluorophenyl) methanamine (0.12 mL, 0.92 mmol) and N, N-diisopropylethylamine (0.4 mL, 2.3 mmol) , and the mixture was stirred at rt for 12 hours. The reaction mixture was washed with water (20 mL ¡Á 3) . The organic layer was dried over anhydrous sodium sulfate. The organic solvent was removed and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) 6/1) to give the title compound as a white solid (188 mg, 46) .

The chemical industry reduces the impact on the environment during synthesis 15205-15-9. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Bing; YU, Tianzhu; ZHANG, Yingjun; ZHANG, Xiangyu; ZHANG, Shiguo; CHENG, Changchung; ZHANG, Jiancun; WO2015/161830; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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

4863-91-6, 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 4863-91-6 as follows.

General procedure: To a solution of 3-chloroaniline 5a (37mg, 0.33mmol) in H2O (10mL cooled to-5C) was added 0.2mL of 2N HCl (aq.). To the resulting acidic aniline solution, 1N solution of sodium nitrite (0.33mL, 0.33mmol) was added dropwise to generate the aryldiazonium salt solution 6a. To the aryldiazonium salt solution was added sodium acetate (54mg, 0.66mmol), followed by 1mL solution of crude 3-oxo-3-(3-phenylisoxazol-5-yl)propanenitrile 4a (88mg, 0.33mmol) in ethanol. The reaction mixture was stirred at 0C for 5min, and then poured onto H2O (10mL) and extracted with ethyl acetate (20mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by short column chromatography on silica gel, eluting with hexane/ethyl acetate (2/1) to provide the desired product 7 (67mg, 50% for two steps from 3a) as a yellow solid.

According to the analysis of related databases, 4863-91-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Ye, Na; Zhu, Yingmin; Liu, Zhiqing; Mei, Fang C.; Chen, Haiying; Wang, Pingyuan; Cheng, Xiaodong; Zhou, Jia; European Journal of Medicinal Chemistry; vol. 134; (2017); p. 62 – 71;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 13526-66-4 name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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. 13526-66-4

To a solution of 3-bromo-6-chloroimidazo[1 ,2-b]pyridazine (232.0 mg, 1 .00 mmol) in THF (5 ml_) was added EtMaBr (1 M in THF, 1 .50 ml_, 1 .50 mmol) at -10 QC. After stirring at -10 QC for 1 h, i -methyl-I H-indazole-5-carbaldehyde (240.0 mg, 1.50 mmol) was added. The mixture was allowed to warm to rt slowly and stirred for 2 h. The reaction was quenched with saturated NH4CI solution and concentrated under reduced pressure. The residue was diluted with water and extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was washed with DCM to give the title compound as a white solid (230 mg, 70 %). 1H-NMR (400MHz, DMSO-Cf6) delta ppm 8.21 (d, 1 H), 8.02 (s, 1 H), 7.81 (s, 1 H), 7.59 (d, 1 H), 7.56 (s, 1 H), 7.49 (d, 1 H), 7.35 (d, 1 H), 6.29 (d, 1 H), 6.21 (d, 1 H), 4.02 (s, 3H). LCMS (method A): [MH]+ = 314, tR = 4.44 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, and friends who are interested can also refer to it.

Reference:
Patent; NOVARTIS AG; DAI, Miao; FU, Xingnian; HE, Feng; JIANG, Lei; LI, Yue; LIANG, Fang; LIU, Lei; MI, Yuan; XU, Yao-chang; XUN, Guoliang; YAN, Xiaoxia; YU, Zhengtian; ZHANG, Ji, Yue; WO2011/20861; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics