Author: Jessica.F

Some common heterocyclic compound, 54314-84-0, name is ((3-Bromopropoxy)methyl)benzene, molecular formula is C10H13BrO, 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. 54314-84-0

b 1-(3-Benzyloxy-propyl)-5-fluoro-indole-3-carboxylic acid To a solution of a) (0.86 g, 4.45 mmol) and benzyl 3-bromopropyl ether (0.78 mL, 4.45 mmol) in dry DMF (20 mL) was added potassium carbonate (2.46 g, 17.8 mmol), and the mixture was stirred under nitrogen at room temperature overnight. The mixture was partitioned between water and ethyl acetate and the organic phase was washed with water followed by brine and concentrated. The residue was dissolved in ethanol (15 mL) and sodium hydroxide in water (25percent, 50 mL) was added. The reaction mixture was heated at 90¡ã C. for 2 hours, cooled and washed with ethyl acetate. After acidification of the aqueous phase with hydrochloric acid, the product was extracted with ethyl acetate twice. The organic layers were washed with brine, dried and concentrated affording the sub-title product as an off-white solid (1.25 g, 86percent). 1H NMR (400 MHz, CDCl3): delta7.91 (1H, s); 7.87 (1H, dd); 7.36-7.25 (6H, m); 7.01 (1H, dt); 4.46 (2H, s); 4.30 (2H, t); 3.38 (2H); 2.15-2.11 (2H, m).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 54314-84-0, its application will become more common.

Reference:
Patent; Astrazeneca AB; US6492406; (2002); B1;,
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349-65-5, A common heterocyclic compound, 349-65-5, name is 2-Methoxy-5-(trifluoromethyl)aniline, molecular formula is C8H8F3NO, 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.

Synthesis of N-(2-Methoxy-5-(trifluoromethyl)phenyl)-N’-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) Urea To a solution of 2-methoxy-5-(trifluoromethyl)aniline (0.15 g) in anh CH2Cl2 (15 mL) at 0 C. was added CDI (0.13 g). The resulting solution was allowed to warm to room temp. over 1 h, was stirred at room temp. for 16 h, then was treated with 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline (0.18 g). The resulting yellow solution was stirred at room temp. for 72 h, then was treated with H2O (125 mL). The resulting aqueous mixture was extracted with EtOAc (2*150 mL). The combined organics were washed with a saturated NaCl solution (100 mL), dried (MgSO4) and concentrated under reduced pressure. The residue was triturated (90% EtOAc/10% hexane). The resulting white solids were collected by filtration and washed with EtOAc. The filtrate was concentrated under reduced pressure and the residual oil purified by column chromatography (gradient from 33% EtOAc/67% hexane to 50% EtOAc/50% hexane to 100% EtOAc) to give N-(2-methoxy-5-(trifluoromethyl)phenyl)-N’-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea as a light tan solid (0.098 g, 30%): TLC (100% EtOAc) Rf 0.62; 1H NMR (DMSO-d6) delta2.76 (d, J=4.8 Hz, 3H), 3.96 (s, 3H), 7.1-7.6 and 8.4-8.6 (m, 11H), 8.75 (d, J=4.8 Hz, 1H), 9.55 (s, 1H); FAB-MS m/z 461 ((M+H)+).

The synthetic route of 349-65-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER CORPORATION; US2003/144278; (2003); A1;,
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402-07-3, The chemical industry reduces the impact on the environment during synthesis 402-07-3, name is 4-Bromo-3-methoxybenzotrifluoride, I believe this compound will play a more active role in future production and life.

A vial was charged with 6-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)- 3,4-dihydro-2H-benzo[b][l,4]oxazine-7-sulfonamide (107.43 mg, 0.216 mmol), l-bromo-2-methoxy-4-(trifluoromethyl)benzene (Sigma-Aldrich, St. Loius, MO, 193 mg, 0.757 mmol), Xantphos (25.04 mg, 0.043 mmol), Pd2(dba)3 (19.82 mg, 0.022 mmol), and cesium carbonate (212 mg, 0.649 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (2164 mu) was added. The vessel was sealed and placed in a 100 C heating bath for 20 h. The mixture was cooled to room temperature, diluted with EtOAc, and filtered through celite. The filtrate was concentrated, and the residue was purified by chromatgraphy on silica gel (12-g Redi-Sep Gold column, 0-50% EtO Ac/Heptane) to give 6-bromo-4-(2-methoxy-4- (trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H- benzo[b][l,4]oxazine-7-sulfonamide (67 mg, 0.100 mmol, 46.2 % yield) as a yellow foam: m/z (ESI) 670.2 (M+H)+

The chemical industry reduces the impact on the environment during synthesis 4-Bromo-3-methoxybenzotrifluoride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AMGEN INC.; BOEZIO, Christiane; BOEZIO, Alessandro; BREGMAN, Howard; CHAKKA, Nagasree; COATS, James R.; COPELAND, Katrina W.; DIMAURO, Erin F.; DINEEN, Thomas; GAO, Hua; LA, Daniel; MARX, Isaac E.; NGUYEN, Hanh Nho; PETERSON, Emily Anne; WEISS, Matthew; WO2013/122897; (2013); 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 111-95-5 as follows. 111-95-5

Bis(2-methoxyethyl)amine (9.0 mL, 60.8 mmol, 1.8 eq.) was added dropwise to a solutionof PCl3 (3.0 mL, 34.3 mmol) in dry hexane (90 mL) under N2 at 0 C. The resulting white slurrywas stirred at 20 C for 1 h, filtered and washed with hexanes (3x 100 mL). The solvent wasremoved (rotavap) and the residue distilled under reduced pressure (125 C, 100 mmHg). Theproduct was isolated as a colorless clear liquid (5.14 g, 64%).Data for 29a:1H-NMR: (500 MHz, CDCl3)delta 3.33 (s, 6 H, OCH3), 3.49 (s, 8 H, 1-H, 2-H).13C-NMR: (125 MHz, CDCl3)delta 48.6 (d, J = 16.8 Hz), 58.9, 71.1 (d, J = 2.6 Hz).31P NMR: (200 MHz, CDCl3)delta -84.2.

According to the analysis of related databases, 111-95-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Boese, Dietrich; Denmark, Scott E.; Synlett; vol. 29; 4; (2018); p. 433 – 439;,
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The chemical industry reduces the impact on the environment during synthesis 1535-73-5, name is 3-Trifluoromethoxyaniline, I believe this compound will play a more active role in future production and life. 1535-73-5

Example 61 : 6-(6-Amino-pyrimidin-4-ylsulfanyl)-naphthalene-1-carboxylic acid (3- trifluoromethoxy-phenvP-amide; To 95 mg (0.32 mMol) 6-(amino-pyrimidin-4-ylsulfanyl)-naphthalene-1-carboxylic acid, 85 mg(0.48 mMol) 3-trifluoromethoxy-aniline, 446 mul (3.2 mMol) Et3N and 4 mg (0.03 mMol) DMAP EPO in 3 ml DMF, 0.37 ml (0.63 mMol) propylphosphonic anhydride are added. After 3 h at rt, the reaction mixture is worked up as described for Ex. 58, yielding the title compound: m.p.: 197- 199 ¡ãC; MS: [M+1]+ = 457.

The chemical industry reduces the impact on the environment during synthesis 1535-73-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2006/59234; (2006); A2;,
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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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