Month: November 2020

19056-40-7, name is 4-Bromo-3-methoxyaniline, belongs to ethers-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. 19056-40-7

Step 1. 5-({[4-bromo-3-(methyloxy)phenyl]amino}methylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione: 2,2-dimethyl-1,3-dioxane-4,6-dione (8.5 g, 58 mmol) in trimethyl orthoformate (50 mL, 450 mmol) was refluxed at 105 C for 1 hr. 4-Bromo-3-methoxyaniline (10.5 g, 50.4 mmol) was then added and refluxing was continued for and additional hour. The suspension was filtered, and the solid was washed with MeOH and vacuum dried to yield 5-({[4-bromo-3-(methyloxy)phenyl]amino}methylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (17 g, 49 mmol, 96 % yield). 1H NMR (400 MHz, DMSO-d) delta ppm 1.68 (s, 6H), 3.90 (s, 3H), 7.11 (dd, J = 8.6 Hz, 2 Hz, 1H), 7.43 (d, J= 2 Hz, 1H), 7.59 (d, J= 8.6 Hz, 1H), 8.64 (s, 1H), 11.23 (br. s., 1H).

Statistics shows that 19056-40-7 is playing an increasingly important role. we look forward to future research findings about 4-Bromo-3-methoxyaniline.

Reference:
Patent; GlaxoSmithKline Intellectual Property Development Limited; BURY, Michael, Jonathan; CASILLAS, Linda, N.; CHARNLEY, Adam, Kenneth; HAILE, Pamela, A.; MARQUIS, Robert, W., Jr.; MEHLMANN, John, F.; ROMANO, Joseph, J.; SINGHAUS, Robert, R.; WANG, Gren, Z.; (83 pag.)EP2680844; (2016); B1;,
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2752-17-2, These common heterocyclic compound, 2752-17-2, name is 2,2′-Oxydiethanamine, 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.

General procedure: Diester1 (1mmol) and the appropriate diamine2-6 (1mmol) were dissolved in dry methanol (50mL) and sodium methoxide (2mmol) was added. A mixture was stirring for 72hat room temperature. After completion of the reaction (controlled by TLC), the solvent was evaporated under reduced pressure and the oily residue was purified by column chromatography (1-5% MeOH in CH2Cl2). All the macrocyclic products obtained in this way are colourless solids, stable to air. 4.2.1 Macrocycle (R)-714b (0010) Yield: 60% (282mg); [alpha]D25 +86.4 (c=0.1, CH2Cl2); Mp. 245-246C; 1H NMR (400MHz, CDCl3):delta=8.02 (d, J=9.0Hz, 2H), 7.90 (d, J=8.2Hz, 2H), 7.45-7.21 (m, 6H), 7.07 (d, J=8.5Hz, 2H), 6.41 (br s, 2H), 4.60 (d, J=15.6Hz, 2H), 4.36 (d, J=15.6Hz, 2H), 3.71-3.56 (m, 2H), 3.51-3.39 (m, 2H), 3.38-3.27 (m, 2H), 2.97-2.86 (m, 2H); 13C NMR (100MHz, CDCl3):delta=168.5, 152.7, 133.6, 130.2, 129.8, 128.1, 127.2, 125.0, 124.6, 119.6, 114.1, 68.9, 68.7, 38.5; IR (film) 3423, 3294, 3056, 2914, 2866, 1674, 1533, 1507, 1273, 1213, 1094, 808, 735cm-1.

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 2752-17-2.

Reference:
Article; Pikus, Grzegorz; Jurczak, Janusz; Tetrahedron; vol. 72; 16; (2016); p. 1928 – 1932;,
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366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-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. 366-99-4

To a stirred suspension of 3-fluoro-p-anisidine (3.00 g, 21 mmol) in CH2Cl2 (10 mL) is added acetic anhydride (2.0 mL, 21 mmol) over 1 h while maintaining the temperature between 25-30¡ã C. using a cold water bath. The solution is then stirred for 2 h at 25¡ã C. Additional 1 mL of acetic anhydride is added to the solution, which is then stirred for an additional 2 h. Hexane (30 mL) is slowly added to the mixture over 1 h. The product is collected by filtration, concentrated in vacuo and dried in oven to give 3.40 g (90percent yield) of N-(3-fluoro-4-methoxyphenyl)acetamide as tan crystals. 1H NMR (400 MHz, CDCl3) delta 7.41, 7.19, 7.11, 6.90, 3.87, 2.16. In a 100 mL, three-necked flask equipped with a thermometer and a dropping funnel chilled in an ice-salt bath, N-(3-fluoro-4-methoxyphenyl)acetamide (3.0 g, 16 mmol) is dissolved in 98percent sulfuric acid, care being taken that the temperature does not rise above 5¡ã C. To this solution 2.6 mL of nitric acid is added dropwise at such a rate that the temperature does not rise above 5¡ã C. After all the nitric acid is added, the viscous orange mass is poured onto 50 g of cracked ice and the mixture is thoroughly stirred. The yellow crystals that separate are filtered off and thoroughly washed with water to yield 3.33 g (89percent yield) of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide as yellow crystals. 1H NMR (400 MHz, DMSO-d6) delta 10.60, 10.17, 7.75, 7.73, 7.62, 7.59, 4.03, 3.92, 2.06. A suspension of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide (3.0 g, 13 mmol) in 38 mL of water, 38 mL of HCl and 15 mL of ethanol is refluxed for 30 minutes. On cooling, crystals that separate are recrystallized from ethanol to yield 0.71 g (29percent yield) of 5-fluoro-4-methoxy-2-nitroaniline as red crystals. 1H NMR (400 MHz, CDCl3) delta 7.68, 6.56, 6.04, 3.87. Example 603 is obtained according to Method F, making non-critical modifications. Yield 60percent. HRMS (ESI) calcd for C12H11FN4O5+H 311.0792 found 311.0798.

Statistics shows that 366-99-4 is playing an increasingly important role. we look forward to future research findings about 3-Fluoro-4-methoxyaniline.

Reference:
Patent; Piotrowski, David W.; Rogers, Bruce N.; McWhorter JR., William W.; Walker, Daniel Patrick; Corbett, Jeffrey W.; Groppi JR., Vincent E.; Rudmann, Daniel G.; US2003/236287; (2003); A1;,
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60792-79-2, Name is 2,2′-Oxybis(ethylamine) dihydrochloride, 60792-79-2, belongs to ethers-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.

A suspension of 0.2 M 2,2′-oxydiethylamine dihydrochloride (0.247 gm, 1.35 mmole) and 0.4 M DIEA (0.47 ml, 2.7 mmole) in 4.5 DMF was added to 3-nitro-1,8-naphthalic anhydride (0.018 gm, 0.073 mmole) and heated at 150 C with microwave treatment under nitrogen for 5 minutes. The mixture was cooled, treated with 25 ml 1.3 M aqueous TFA, and concentrated to about 2 ml. The residue was diluted with dichloromethane, washed with sat. NaCl, dried over MgSO4, and concentrated under vacuum to give N- aminoethylethoxy-3-nitro-1,8 naphthalimide 7. MS m/z 330 (M + H)+.

Statistics shows that 2,2′-Oxybis(ethylamine) dihydrochloride is playing an increasingly important role. we look forward to future research findings about 60792-79-2.

Reference:
Patent; GENENTECH, INC.; WO2006/60533; (2006); A2;,
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588-96-5, A common compound: 588-96-5, name is p-Bromophenetole, belongs to ethers-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

General procedure: The Teflon-lined sealed tube (20 mL) was charged with a 1,4-dioxane solution of sodium fluoroalkoxide RFONa [freshly prepared from fluoroalkanol RFOH (3.3(n + 1) mmol) and Na (3.0 (n + 1) mmol) in 1,4-dioxane (5 mL)], unactivated arylbromide ArBrn (3.0 mmol), CuBr (0.3n mmol) and DMF (3.0n mmol). The sealed tube was heated to 110 C and stirred for 6 h. After the completion of reaction, the concentration of the mixture in vacuo gave a residue, to which was added methyl tert-butyl ether (MTBE, 20 mL) and diluted hydrochloric acid (10 mL, 1.0 mol/L). The organic phase was separated, and the aqueous phase was extracted with MTBE (10 mL 9 3). The combined organic layer was dried over anhydrous MgSO4, andthen concentrated in vacuo to supply a crude product. Lastly, the purification of the crude product provided the desired product via column chromatography on silica gel (eluents: petroleum ether/ethyl acetate 20:1).

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, p-Bromophenetole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Guo, Ying; Li, Yu-Dao; Chen, Cheng; Zhao, Jian-Hong; Liu, Hong-Wei; Liao, Dao-Hua; Ji, Ya-Fei; Research on Chemical Intermediates; vol. 42; 3; (2016); p. 2525 – 2537;,
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701-07-5, name is 2-(2′-Bromophenoxy)propane, belongs to ethers-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. 701-07-5

N-{2-chloro-2′-[(l-methyIethyl)oxy]-4-biphenylyI}-2-[4~(ethylsuIfonyI)phenyl]acetamideA mixture of l-bromo-2-[(l-methylethyl)oxy]benzene (38 mg), N-[3-chloro-4-(4,4,5,5- tetramethyl-l}3,2-dioxaborolan-2-yl)phenyl]-2-[4-(ethylsulfonyl)phenyl]acetamide (intermediate 6b, 90 mg), PdCl2(dppf)-CH2Cl2 adduct (10 mg) and Cs2C03 (69.1 mg) in acetonitrile (1.5 mL) and water (0.5 mL) was sealed in a vessel and heated in die microwave at 100C for 30 mins. The reaction mixture was filtered through celite. The filtrate was concentrated under reduced pressure, and the residue was purified by MDAP to afford N-{2-chloro-2′-[(l-methylethyl)oxy]-4-biphenylyl}-2-[4- (etliylsulfonyl)phenyl]acetamide (12 mg) as a yellow solid. ?-NuMuKappa (600 MHz, DMSO-c ) delta ppm 1.11 (m, 9H), 3.28 (q, J= 7.2 Hz, 2H), 3.83 (s, 2H), 4.51 (m, 1H), 6.96 (t, J= 7.8 Hz, 1H), 7.09 (m, 2H), 7.22 (d, J= 6.4 Hz, 1H), 7.33 (m, 1H), 7.48 (m, 1H), 7.63 (d, J= 7.8 Hz, 2H), 7.86 (d, J= 7.8 Hz, 2H), 10.49 (s, 1H); MS(ES+) m/z Ml (MH^>.

Statistics shows that 701-07-5 is playing an increasingly important role. we look forward to future research findings about 2-(2′-Bromophenoxy)propane.

Reference:
Patent; GLAXO GROUP LIMITED; WANG, Yonghui; CAI, Wei; LIU, Qian; MENG, Qinghua; CHENG, Yaobang; YANG, Ting; ZHANG, Guifeng; XIANG, Jianing; WU, Chengde; WO2013/29338; (2013); A1;,
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Adding some certain compound to certain chemical reactions, such as: 20469-65-2, name is 1-Bromo-3,5-dimethoxybenzene, 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 20469-65-2. 20469-65-2

As follows are specific steps of: adding 3,5-dimethoxy-bromobenzene (1.74 g, 8.0 mmol, 1.0 equivalent (hereinafter referred to as ?eq?)) and a catalyst PdCl(PPh)(281 mg, 0.4 mmol, 0.05 eq) into a 100 mL Schlenk reaction flask; performing a cycle of vacuumizing and filling nitrogen gas in the flask for three times; adding dried and redistilled 1,2-dichloroethane (20 ml), triethylamine (7 ml, 40 mmol, 5.0 eq) and pinacol borane (HBpin) (3.5 ml, 24.0 mmol, 3.0 eq) into the reaction flask by a syringe; heating the reaction system to 90 C. and performing a reflux reaction for 4 hours; cooling the reaction system down to room temperature, then pouring the reaction solution into 20 ml water to terminate the reaction; extracting aqueous phases with ethyl acetate for several times and combining organic phases; washing the organic phases with a saturated saline solution and water for one time, respectively; drying with anhydrous magnesium sulfate and spin-drying the solvent; recrystallizing an obtained product in n-hexane/ethyl acetate to obtain a 1.8 g white solid with the yield of 85%. H NMR (400 MHz, CDCl) delta (ppm) 7.03 (s, 2H, benzene), 6.90 (s, 1H, benzene), 3.84 (s, 6H, -OCH3), 1.33 (s, 12H, -CH3).

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 1-Bromo-3,5-dimethoxybenzene.

Reference:
Patent; TECHNICAL INSTITUTE OF PHYSICS AND CHEMISTRY OF THE CHINESE ACADEMY OF SCIENCES; Li, Yi; Hao, Qingshan; Chen, Jinping; Zeng, Yi; Yu, Tianjun; US2015/353468; (2015); A1;,
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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 658-89-9 as follows. 658-89-9

To a solution of 4-trifluoromethoxy-benzene-1, 2-diamine 2 (4.5 g, 23.4 itimol) and triethylamine (5.0 g, 49.5 iranol) in methylene chloride (100 ml) was added dropwise a solution of diphosgene (2.4 g, 12.1 mmol) in methylene chloride (10 ml) at 0-5C. The resulting suspension was stirred for 1 h at rt and filtered. The collected white solid was washed with water and dried to give 3.85 g (75%), mp 260-2620C.

According to the analysis of related databases, 658-89-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES, LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2006/50148; (2006); A2;,
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Some common heterocyclic compound, 2930-05-4, name is 2-((Benzyloxy)methyl)oxirane, molecular formula is C10H12O2, 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. 2930-05-4

General procedure: In a 20 mL pressure tube (for volatile amines) was combined epoxide (1.0 mmol, 1.0 equiv) and amine (1.5 mmol, 1.5 equiv) 6.7 mL of reagent grade DMF. The reaction vessel fitted with a stirbar, sealed, and heated at 60C for 12 h after which the vessel was allowed to cool to ambient temperature (not necessary for reactions not ran in pressure vessels) before receiving deionized water (50 equiv) in one portion. The vessel was resealed and stirred at 60C for an additional 12 h. Solvent was removed on a rotary evaporator (22.5 mbar at 35C) and the crude residue loaded directly onto a silica gel column.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2930-05-4, its application will become more common.

Reference:
Article; Lizza, Joseph R.; Moura-Letts, Gustavo; Synthesis; vol. 49; 6; (2017); p. 1231 – 1242;,
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Adding some certain compound to certain chemical reactions, such as: 19056-41-8, name is 3-Bromo-4-methoxyaniline, 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 19056-41-8. 19056-41-8

2-Amino-3′-methoxybenzophenone. In a flame-dried round bottom flask, anthranilic acid N-methoxyl-N-methylamide (8.00 g, 44.4 mmol) and m-bromoanisidine (8.31 g, 44.4 g) were dissolved in 250 mL of THF and the resulting solution was cooled to -78 C. With vigorous stirring, 2 equiv of nBuLi in hexanes (55.5 mL, 1.6 M, 88.8 mmol) was added dropwise by a syringe pump at 0.6 mL/min. After 20 min, 80 mL of 1 N hydrochloric acid was carefully added, the mixture was extracted with ethyl acetate (600 mL), and the ethyl acetate was washed with water (300 mL) and brine (300 mL), dried over sodium sulfate and concentrated in vacuo. Flash chromatography with 95:5 hexanes/ethyl acetate afforded 6.92 g (69% yield) of 2-amino-3′-methoxybenzophenone as a 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 3-Bromo-4-methoxyaniline.

Reference:
Patent; Board of Regents, The University of Texas System; The Regents of the University of California; US6100254; (2000); A;,
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