Month: January 2021

Application of 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.

Preparation of 1- {4- [2-(4-chIorophenoxy)phenylamino] -piperidin-1 -yl}-2- methylpropan-1-one STX1701 C21H25ClN2O2, MW: 372.8939To a solution of 2-(4-chlorophenoxy)phenylamine (100 mg3 0.45 mmol), l-isobutyryl-4- piperidone (144 mg, 0.735 mmol) and acetic acid (147 mg, 2.45 mmol) in DCE (1.5 ml) was added sodium triacetoxyborohydride (260 mg, 1.23 mmol). This solution was then heated at 1000C for 15 minutes in a CEM discover microwave (fixed hold time set to on).The reaction mixture was then quenched with saturated aqueous sodium bicarbonate solution (5 ml) and extraction with ethyl acetate (3 x 5 ml) followed. The combined organics were concentrated in vacuo and purification by flash chromatography proceeded(eluant: 8:2 hexane: ethyl acetate) to provide the title compound as a transparent oil (44 mg, 26%). 1HNMR (270 MHz, CDCl3): delta 1.10 (6H, d, J= 6.7 Hz, CH(CH3)2), 1.25-1.35(2H, m, 2 x CH), 2.03-2.27 (2H, m, 2 x CH), 2.76-2.85 (2H, m, 2 x CH)3 3.18 (IH, t, J=11.4 Hz, CH), 3.48-3.60 (IH, m, CH), 3.83-3.88 (IH, bd, J = 13.9 Hz3 CH)3 3.97-4.12 (IH, m, NH), 4.41-4.46 (IH, bd, J= 13.9 Hz, CH), 6.61-6.67 (IH, td, J- 1.2, 0.7, 7.7 Hz3 EPO ArH)5 6.74-6.77 (IH, dd, J= 1.2, 8.2 Hz, ArH), 6.79-6.82 (IH3 dd, J= 1.5, 7.9 Hz, ArH), 6.85-6.90 (2H, m, ArH), 7.01-7.07 (IH, td, J= 1.2, 0.8, 7.2 Hz, ArH), 7.20-7.25 ppm (2H, m, ArH). LCMS: M+R: 373.49 HPLC: 93.75% (2.692 min, isocratic 90% acetonitrile, 10% water at 1 ml/min).

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; STERIX LIMITED; WO2007/3934; (2007); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 452-73-3, 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. 452-73-3 name is 2-Chloro-4-fluoro-1-methylbenzene, 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 1 Preparation of 2-chloro-4-fluorobenzyl bromide A solution of bromine (7.10 ml) in carbon tetrachloride (70 ml) was added slowly over a period of 3 hours to a solution of 2-chloro-4-fluorotoluene (20.0 g) in carbon tetrachloride (80 ml) maintained at the reflux temperature and irradiated by light from a tungsten lamp (200 watt). After the addition was completed the mixture was heated at the reflux temperature with irradiation until the colour had been discharged (ca.1 hour). The solvent was then removed by evaporation under reduced pressure and the residual oil distilled to yield 2-chloro-4-fluorobenzyl bromide (80% pure, 18.0 g) b.p. 110-120 C./15 mm Hg.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-4-fluoro-1-methylbenzene, and friends who are interested can also refer to it.

Reference:
Patent; Imperial Chemical Industries PLC; US4567199; (1986); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 108-37-2, 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. 108-37-2, name is 1-Bromo-3-chlorobenzene, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of diisopropylamine (76 niL, 0.4 mol) in anhydrous THF (664 rnL) and n-hexane (220 rnL) was added 2.5 M n-BuLi (160 rnL, 0.4 mol) dropwise at -78 0C over 1 h. The mixture was stirred for 1 h at -78 0C and a solution of 1-bromo- 3-chlorobenzene (76 g, 0.4 mol) in anhydrous THF (300 mL) was added dropwise at – 78 0C. After stirring for an additional 1 h at the same temperature, a solution of iodine (101 g, 0.4 mol) in anhydrous THF (400 mL) was added dropwise at -78 0C. The temperature was raised from -78 0C to rt during 2 h. After stirring for 18 h at rt, the mixture was concentrated in vacuo to give the crude product (120 g) which was distilled under reduced pressure to give l-bromo-3-fluoro-2-iodobenzene (115 g, 91%). 1H NMR (400MHz, CDCl3): 7.12-7.18 (t, IH), 7.35-7.41 (dd, IH), 7.49-7.54 (dd, IH); MS (E/Z): 317 (M+H+)

The chemical industry reduces the impact on the environment during synthesis 1-Bromo-3-chlorobenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; VITAE PHARMACEUTICALS, INC.; WO2008/124577; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 175205-77-3, name is 4-Chloro-2-(trifluoromethoxy)aniline, 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 175205-77-3, Computed Properties of C7H5ClF3NO

Synthesis of 2-chloro-N-(4-chloro-2-(trifluoromethoxy) phenyl)-5-methoxypyrimidin-4-amine [0441] To a stirred solution of sodium hydride (1.3 g, 55.84 mmol) in DMF (50 mL) under argon atmosphere were added 2, 4-dichloro-5-methoxypyrimidine (5 g, 27.93 mmol) and 4-chloro-2-(trifluoromethoxy) aniline (5.9 g, 27.93 mmol) at 0C. The reaction mixture was warmed to RT for 4 h. After consumption of the starting materials (monitored by TLC), the reaction was diluted with water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 10-30% EtOAc:hexanes to afford 2-chloro-N-(4-chloro-2-(trifluoromethoxy) phenyl)-5-methoxypyrimidin-4-amine (4.5 g, 45%) as a pale yellow solid. 1H-NMR (DMSO-< 5, 500 MHz): delta 9.23 (s, 1H), 8.00 (s, 1H), 7.67-7.60 (m, 2H), 7.53 (d, 1H), 3.96 (s, 3H); LCMS: 355 (M+1); (column; X-Select CSH C- 18 (50 3.0 mm, 3.5 mupiiota); RT 4.90 min 0.05% Aq TFA: ACN; 0.80 mL/min); UPLC (purity): 94.2%; (column; Acquity UPLC BEH C-18 2.1 X 50 mm, 1.7 mupiiota); RT 2.86 min. ACN: 0.025% Aq TFA; 0.5 mL/min; TLC: 30% EtOAc/hexane (R/. 0.3). At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Chloro-2-(trifluoromethoxy)aniline, and friends who are interested can also refer to it. Reference:
Patent; FORUM PHARMACEUTICALS INC.; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; MCRINER, Andrew, J.; WO2015/66697; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 202925-07-3, These common heterocyclic compound, 202925-07-3, name is 2-Chloro-1-fluoro-4-methoxybenzene, 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.

To a solution of 3-chloro-4-fluoroanisole (28.5 g, 178 mmol) in i-butyl methyl ether (200 mL, dried over anhydrous MgS04) at -78 C was added 2.5 M n-butyl lithium in hexanes (107 mL, 267.5 mmol). After 3 h, methyl formate (18.76 mL) was added drop-wise while keeping the temperature below -60 C. The reaction mixture was quenched with sat. aq. ammonium chloride (250 mL) after 45 minutes and the organic layer was separated. The aq. layer was extracted with ethyl acetate (2×100 mL) and the combined organic layer was washed with water (200 mL) followed by brine, dried (Na2S04) and concentrated to give a residue which on trituration with hexanes gave solids. The solids were filtered, taken again in hexanes and heated over steam bath. It was cooled, the light yellow desired product filtered and air dried to give the title compound. 1H NMR (400 MHz, CDCI3): delta = 10.48 (d, J = 0.8 Hz, 1 H), 7.31 (dd, J = 9.4, 7.8 Hz, 1 H), 6.88 (dd, J = 7.8, 3.8 Hz, 1 H), 3.92 (s, 3H). 13C NMR (100.6 MHz, CDCI3, DEPT135): delta = 188.36 (+, JCF = 2.4 Hz), 158.01 (Cquart, JCF = 2.0 Hz), 152.73 (Cquart, JCF = 243.0 Hz), 122.87 (Cquart), 122.85 (Cquart, JCF = 18.4 Hz), 121 .01 (+, JCF = 24.5 Hz), 1 10.65 (+, JCF = 6.9 Hz), 56.57 (+).

The synthetic route of 202925-07-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OSI PHARMACEUTICALS, LLC; JIN, Meizhong; MULVIHILL, Mark, J.; STEINIG, Arno, G.; WANG, Jing; WO2012/158658; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 64628-73-5, name is 3-Chloro-4-(trifluoromethoxy)aniline, 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 64628-73-5, Product Details of 64628-73-5

General procedure: A dry, 50 mL round bottom flask was charged with a magnetic stir bar then sealed with a septum and flushed with nitrogen. To this was added the salicylic acid derivative (2.0 mmol) and dichloromethane (10 mL). While stirring, SOCl2 (10 mmol) was added dropwise, followed by dimethylformamide (0.05 mmol), and the mixture was allowed to stir at room temperature under nitrogen for 12 hours. At this point, the mixture was concentrated under vacuum to afford the solid acid chloride derivative which was used immediately without further purification. The flask containing the acid chloride was then re-sealed with a septum and placed under a nitrogen atmosphere, and its contents were re-suspended in fresh dichloromethane (20 mL). While stirring, the aniline derivative (4.0 mmol) was added and the resulting opaque mixture was stirred for an additional 18 h. At this point, the mixture was quenched with ice water (5 mL) and phases were separated using a separatory funnel. The aqueous layer was extracted twice with dichloromethane (20 mL) then the organic layers were combined and washed with brine (40 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated under vacuum to afford a crude solid residue. This residue was then re-suspended in dichloromethane (10 mL) and adsorbed onto silica gel (1 g), then chromatographed on a 12 g silica gel column using a solvent gradient of 0-40% ethyl acetate in hexanes over 25 min. The product-containing fractions were combined then concentrated under vacuum to afford the purified salicylamide derivative.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Chae, Hee-Don; Cox, Nick; Capolicchio, Samanta; Lee, Jae Wook; Horikoshi; Kam, Sharon; Ng, Andrew A.; Edwards, Jeffrey; Butler, Tae-Leon; Chan, Justin; Lee, Yvonne; Potter, Garrett; Capece, Mark C.; Liu, Corey W.; Wakatsuki, Soichi; Smith, Mark; Sakamoto, Kathleen M.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 16; (2019); p. 2307 – 2315;,
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. 1871-57-4, name is 3-Chloro-2-chloromethyl-1-propene, A new synthetic method of this compound is introduced below., Recommanded Product: 3-Chloro-2-chloromethyl-1-propene

Compound 1 (100 g, 0.8 mol)With 18-crown-6 ether (5 g)And pinacol (8 g)Dissolved in bromoform (400 g)An aqueous solution of sodium hydroxide (30% by mass, 1.0 L) was added dropwise at 10 C to 25 C,The reaction was then stirred at room temperature for 24 hours.TLC (petroleum ether / ethyl acetate = 10/1, volume ratio, the same below) shows the end of the reaction. The reaction system was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 5/1 to 1/1) to give compound 2 (168 g) in a yield of 70.7%

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; Shanghai Syn-The-All medical research and development Co . ltd; Shanghai Syn-The-All Pharmaceutical Co. Ltd.; CHANGZHOU HEQUAN PHARMACEUTICAL CO LTD; Wan, xiaojun; Bi, zengliang; Wang, HaiHui; Shen, wanjun; Peng, Yannan; Cheng, Yuan; Shao, WenQing; Chen, YuYan; Yuan, Xiaobin; Yu, LingBo; Li, Lei; Ha, Weijie; Chai, YanPing; Zhou, LeLe; Wu, Xuan; Zhu, Xiwen; Ma, Kunyan; Chen, Yuanli; He, Zhenmin; Ma, RuJian; Chen, Minzhang; Fu, XiaoYong; Wang, Wengui; (5 pag.)CN105294442; (2016); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2729-34-2, name is 3,5-Dichloro-4-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. Formula: C6H4Cl2FN

(3,5-Dichloro-4-fluoro-phenyl)-[l-(4-methoxy-benzyl)-5-morpholin-4-yl-lH-[l,2,4]triazol-3- yl] -amine – In a 2-5 mL microwave vial, 4-(3-bromo-l-(4-methoxybenzyl)-lH-l,2,4-triazol-5-yl)morpholine (133.5 mg, 378 muiotaetaomicron, Eq: 1.00), 3,5-dichloro-4-fluoroaniline (81.6 mg, 454 muiotaetaomicron, Eq: 1.20), sodium tert-butoxide (109 mg, 1.13 mmol, Eq: 3.00), tris(dibenzylideneacetone)dipalladium (0) (20.8 mg, 22.7 muiotaetaomicron, Eq: 0.06) and di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (38.5 mg, 90.7 muiotaetaomicron, Eq: 0.24) were combined. The system was evacuated and recharged with nitrogen (2x). Toluene (1.08 ml) was then added. The mixture was stirred at room temperature for 5 minutes and then heated at 85C for 15 h. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The organic layer was removed, washed with brine, dried (Na2S04) and concentrated over celite. The crude material was purified by flash chromatography (silica gel, SF15-24 g, 20% to 100% EtOAc in hexanes) to gove 90 mg (53%) of desired product.

The synthetic route of 2729-34-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DING, Qingjie; JIANG, Nan; WEIKERT, Robert James; WO2014/135472; (2014); 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. 823-57-4, name is 2-Bromo-5-chloroaniline, This compound has unique chemical properties. The synthetic route is as follows., category: chlorides-buliding-blocks

To a solution of 2-bromo-5-chloroaniline (1.0 eq ) in tetrahydrofuran (0.2 M) at O0C under N2 atmosphere was added dropwise IM NaHMDS (2.5 eq.). The reaction was stirred for 15 minutes at 00C, and a solution of di-tert -butyl dicarbonate in tetrahydrofuran was added. The reaction was warmed to room temperature overnight. The solvent was evaporated, and the resulting residue was quenched with 0.1N HCl aqueous solution. The aqueous suspension was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH.(R). system (ISCO) using 0-5percent ethyl acetate in hexane to give the product as light yellow oil.

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 823-57-4.

Reference:
Patent; IRM LLC; NOVARTIS AG.; WO2009/111337; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 1005-56-7,Some common heterocyclic compound, 1005-56-7, name is O-Phenyl carbonochloridothioate, molecular formula is C7H5ClOS, 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.

(Scheme 1) to 500 mg (1.49mmol) fluorescent dye, 516 mg (2.98mmol) sulfur generation of chlorine phenyl formate (384 mg, 2 . 98mmol) and N, N – diisopropylethylamine (DIPEA) dissolved in 15 ml dichloromethane in, then 25 C stirring reaction under 9h, after steaming and to get the crude product, last-used methylene chloride: methanol=60:1 system carrying out column chromatography separation, get the pure product 647 mg, and the yield is 92

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

Reference:
Patent; University of Jinan; Wang, Yawei; Zhang, Meng; Wu, Liu; Liu, Caiyun; Duan, Qingxia; Wang, Zuokai; Zhu, Baocun; (12 pag.)CN106543097; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics