Month: December 2020

Some common heterocyclic compound, 854391-95-0, name is Bis(4-methoxybenzyl)amine hydrochloride, molecular formula is C16H20ClNO2, 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. 854391-95-0

A solution of 2-(benzylthio)-5-chloropyrazine (0.916 g, 3.87 mmol) in DCM (15 mL, 233 mmol) was treated with water (1.5 mL) and the resultant suspension was cooled to between -5 and o C. Sulfuryl chloride (2.2 mL, 26.2 mmol) was added and the reaction mixture was stirred for 2 hours maintaining the temperature between -5 and o C. A slurry of ice/water (10 mL) was added and the organic phase was collected. The aqueous phase was extracted with DCM (2 x 10 mL) and the combined organic extracts were dried (MgS04) and concentrated in vacuo to afford crude intermediate 5- chloropyrazine-2-sulfonyl chloride as a pale yellow liquid (1.198 g). (1370) A suspension of bis(4-methoxybenzyl)amine hydrochloride (1.198 g, 4.08 mmol) and TEA (1.2 mL, 8.61 mmol) in DCM (15 mL) at o C was treated with a solution of 5- chloropyrazine-2-sulfonyl chloride (0.824 g, 3.87 mmol) in DCM (5 mL) dropwise. The resultant solution was stirred at o C for 15 minutes and then allowed to warm to room temperature for 16 hours. A saturated aqueous NH4C1 solution (10 mL) was added and the organic phase was collected. The aqueous phase was extracted with DCM (2 x 10 mL) and the combined organic extracts were dried (MgS04) and concentrated in vacuo. The crude product was purified by chromatography on silica gel (24 g column, 0-30% EtOAc/isohexane) to afford the title compound (1.312 g, 77 %) as a white solid. (1371) NMR (CDCI3) delta 8.78 (d, J = 1.4 Hz, lH), 8.46 (d, J = 1.4 Hz, lH), 7.11 – 7.07 (m, 4H), 6-79 – 6.75 (m, 4H), 4-43 (s, 4H), 3-79 (s, 6H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 854391-95-0, its application will become more common.

Reference:
Patent; INFLAZOME LIMITED; COOPER, Matthew; MILLER, David; MACLEOD, Angus; VAN WILTENBURG, Jimmy; THOM, Stephen; ST-GALLAY, Stephen; SHANNON, Jonathan; (352 pag.)WO2019/8025; (2019); A1;,
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In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 5414-19-7, name is 1-Bromo-2-(2-bromoethoxy)ethane belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 5414-19-7

[0971] To a DMF (9 mL) solution of Part E (1.08 g, 2.71 mmol) was added K2CO3 (1.12 g, 8.16 mmol), 18-crown-6 (0.21 g, 0.80 mmol), and bis(2-bromoethyl)ether (0.37 mL, 2.9 mmol). The slurry was stirred at 60C. for 72 hr. Additional bis(2-bromoethyl)ether was added at 24 hr (0.4 mmol) and 48 hr (1.2 mmol). The solvent was stripped in vacuo, and the residue was partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was separated, dried over MgSO4, and evaporated to an oil. Recrystallization from diethyl ether produced 0.88 g (69%) of the desired compound in the form of a white solid. LCMS: m/z=469.2 (M+H).

The synthetic route of 5414-19-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Brown, David L.; Carroll, Jeffery N.; Chen, Yiyuan; Fobian, Yvette M.; Freskos, John N.; Gasiecki, Alan F.; Grapperhaus, Margaret L.; Heintz, Robert M.; Hockerman, Susan L.; Kassab, Darren J.; Khanna, Ish K.; Kolodziej, Stephen A.; Massa, Mark A.; McDonald, Joseph J.; Mischke, Brent V.; Mischke, Deborah A.; Mullins, Patrick B.; Nagy, Mark A.; Norton, Monica B.; Rico, Joseph G.; Schmidt, Michelle A.; Stehle, Nathan W.; Talley, John J.; Vernier, William F.; Villamil, Clara I.; Wang, Lijuan J.; Wynn, Thomas A.; US2005/9838; (2005); 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 5414-19-7 as follows. 5414-19-7

Under argon, 100 mg (0.30 mmol) of (4S)-1-(4-aminophenyl)-8-methoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 53.2A) were dissolved in 4 ml of N,N-dimethylacetamide, and 103 mg (0.44 mmol) of 1-bromo-2-(2-bromoethoxyl)ethane and 0.1 ml (0.59 mmol) of diisopropylethylamine were added. The mixture was stirred at 120 C. for three days. The reaction was added to water and extracted three times with ethyl acetate. The solvent was removed on a rotary evaporator and the residue was purified by flash chromatography. This gave 95 mg (79% of theory) of the desired product. [2019] UPLC/MS (Method 2): Rt=1.18 min; m/z=409 (M+H)+ [2020] 1H-NMR (300 MHz, CDCl3): delta=1.07 (d, 3H), 2.72 (dd, 1H), 2.86 (d, 3H), 2.95 (dd, 1H), 3.25 (m 4H), 3.71 (s, 3H), 3.89 (m, 4H), 5.19-5.30 (m, 1H), 6.12 (m, 1H), 6.67 (d, 1H), 6.89 (dd, 1H), 6.92 (d, 2H), 7.15 (d, 1H), 7.51 (d, 2H).

According to the analysis of related databases, 5414-19-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; Siegel, Stephan; Baeurle, Stefan; Cleve, Arwed; Haendler, Bernard; Fernandiez-Montalvan, Amaury Ernesto; Moenning, Ursula; Krause, Sabine; Lejeune, Pascale; Schmees, Norbert; Busemann, Matthias; Holton, Simon; Kuhnke, Joachim; US2015/203483; (2015); A1;,
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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. 157869-15-3 name is 2-((4-Methoxyphenyl)ethynyl)aniline, 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. 157869-15-3

In 15 ml reaction tube are sequentially added into a 1 l (0.3 mmol, 67 mg), [RhCp * Cl2 ]2 (0.015 Mmol, 9.3 mg) and hexafluoroisopropanol (2 ml), in a nitrogen atmosphere of the reaction pipe sealing, in the 120 C stirring for 20 h. After the reaction, the reaction tube to be cooled to the room temperature, adding 10 ml water, then the extraction of ethyl acetate (10 ml ¡Á 3), after the organic phase with water and saturated salt water are successively washing, drying with anhydrous sodium sulfate. Filtering, turns on lathe does, too separating by silica gel column (petroleum ether/ethyl acetate=10/1) to yellow solid product 2 l (44 mg, 65%). The compound of the characterization data are as follows

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-((4-Methoxyphenyl)ethynyl)aniline, and friends who are interested can also refer to it.

Reference:
Patent; Henan Normal University; Fan Xuesen; Jia Ruixue; Zhang Xinying; Li Bin; (19 pag.)CN110105274; (2019); A;,
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57478-19-0, name is 4-(4-(Trifluoromethyl)phenoxy)aniline, 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. 57478-19-0

To a solution of 4-(4-trifluoromethyl-phenoxy)-phenylamine (15.18 g, 60 mmol) and pyridine (7.2 mL, 90 mmol) in dried CH2Cl2 (100 mL) under N2 at 0 C. was added methanesulfonyl chloride (5.22 mL, 66 mmol) dropwise. The mixture was stirred at 0 C. for 1 h and was then poured into CH2Cl2/H2O (100 mL/100 mL). 2N HCl(aq) (30 mL) was added into additional funnel. The organic layer was then washed with H2O (100 mL), brine (100 mL), dried (Na2SO4), and filtered. After removal of solvent, the crude product can be resolidified from Et2O/hexane to give 18.2 g of the titled product (92%) as a pale brown solid. 1H NMR (300 MHz, CDCl3) delta 7.58 (d, J=9.0 Hz, 2H), 7.30 (d, J=9.0 Hz, 2H), 7.04 (d, J=9.0 Hz, 4H), 6.93 (s, 1H, NH), 3.04 (s, 3H); MS (EI) 331 (M+), 330 (M+-1, 100).

Statistics shows that 57478-19-0 is playing an increasingly important role. we look forward to future research findings about 4-(4-(Trifluoromethyl)phenoxy)aniline.

Reference:
Patent; Zhang, Yue-Mei; Xiang, Bangping; Yang, Shyh-Ming; Rhodes, Kenneth; Scannevin, Robert; Jackson, Paul; Chakravarty, Davraj; Fan, Xiaodong; Wilson, Lawrence J.; Karnachi, Prabha; US2008/103129; (2008); A1;,
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1758-46-9, Adding some certain compound to certain chemical reactions, such as: 1758-46-9, name is 2-Phenoxyethylamine, 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 1758-46-9.

To a stirred yellow solution of VII (371.8 mg, 1.089 mmol) in anhydrous THF (10 mL) was added 2-phenoxyethylamine (165 mg, 157 muL, 1,1×1.089 mmol) and then, dropwise, triethylamine (121 mg, 168 muL, 1.1×1.089 mmol). The solution was stirred for 1.5 hours at room temperature. The colorless solution was then diluted with CH2Cl2 and washed with 1N HCl, distilled water, and saturated NaCl. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated. The crude product was purified by column chromatography on silica gel using hexanes/ethyl acetate (1:1, v/v) to yield 260.6 mg (67percent) of a 11 as a clear light yellow oil: Rf=0.39 (hexanes/ethyl acetate, 1:1, v/v); 1HNMR (CDCl3) delta 7.26 (td, 3J=8.0 Hz, 4J=1.1 Hz, 2H), 6.98 (d, 3J=8.0 Hz, 1H), 6.96 (m, 1H), 6.94 (d, 4J=1.0 Hz, 1H), 6.92 (dd, 3J=8.7 Hz, 1H), 6.86 (d, 3J=8.1 Hz, 2H), 5.21 (bs, 1H, NH), 5.06 (s, 2H), 4.03 (t, 3J=5.0 Hz, 2H), 3.80 (s, 3H), 3.59 (q, 3J=5.2 Hz, 2H, NCH2) and 2.29 (s, 3H). Exact mass (EST) calculated for C19H22NO6 [M+H]=360.1442. found 360.1443.

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 1758-46-9.

Reference:
Patent; Laskin, Jeffrey D.; Heck, Diane E.; Lacey, Carl Jeffrey; Aponte, Erik; Huang, Mou-Tuan; Heindel, Ned D.; US2012/59007; (2012); A1;,
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These common heterocyclic compound, 887581-09-1, name is (2-Bromo-5-methoxyphenyl)methanamine, 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. 887581-09-1

General procedure: A 25 mL Schlenk tube wascharged with a magnetic stirrer and DMSO (2.0 mL). Substituted(2-bromophenyl)methylamine (1) (0.5 mmol), amidine hydrochloride (2) (1.0 mmol),CuBr (0.1 mmol, 14.2 mg), and K2CO3 (1.5 mmol, 207 mg) were added to the tube.The mixture was stirred at 80-120 oC under nitrogen atmosphere for 24 h, and thenunder air for 0.5 h. The resulting mixture was cooled to room temperature and filtered,and the solid was washed with ethyl acetate for two times (3 ¡Á 3 mL). The combinedfiltrate was concentrated by the rotary evaporator, and the residue was purified bycolumn chromatography on silica gel using petroleum ether/ ethyl acetate as eluent togive the desired target product.

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 887581-09-1.

Reference:
Article; Liu, Qing; Zhao, Yufen; Fu, Hua; Cheng, Changmei; Synlett; vol. 24; 16; (2013); p. 2089 – 2094;,
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Some common heterocyclic compound, 6851-80-5, name is 1-(2-Methoxyphenyl)-N-methylmethanamine, molecular formula is C9H13NO, 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. 6851-80-5

Step B: To an ice-cooled mixture of the product from Step A (348 mg, 2.3 mmol) and diisopropylethylamine (394 mg, 3.0 mmol) in dichloromethane (10 mL) was added 1-(benzothiophen-5-yl)-2-bromo-ethanone (see Example 96 for preparation) (600 mg, 2.03 mmol). The reaction mixture was stirred at room temperature for 4 hours and then diluted with dichloromethane (100 mL). The mixture was washed with water and brine, dried over sodium sulfate and concentrated to provide the desired product (800 mg, >99% crude yield): ESI-MS m/z=326 [M+H]+. This crude product was used in the next step without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6851-80-5, its application will become more common.

Reference:
Patent; Molino, Bruce F.; Liu, Shuang; Guzzo, Peter R.; Beck, James P.; US2006/52378; (2006); A1;,
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A common heterocyclic compound, 102-52-3, name is 1,1,3,3-Tetramethoxypropane, molecular formula is C7H16O4, 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. 102-52-3.

5-Amino-1H-pyrazole-4-carboxylic acidEthyl ester (3.0 g, 19.3 mmol)In acetic acid (40 mL) and ethanol (10 mL)1,1,3,3-Tetramethoxypropane (3.48 g, 21.4 mmol) was added,The resulting reaction was stirred at 90 C overnight,Cool to room temperature,Concentrate under reduced pressure.The resulting residue was diluted with ethyl acetate (100 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / EA v / v) = 6/1) to give the title compound as a light yellow solid (3.2 g, 85%).

The synthetic route of 1,1,3,3-Tetramethoxypropane has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; (88 pag.)CN104650092; (2017); B;,
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A common compound: 645-36-3, name is 2,2-Diethoxyethanamine, 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. 645-36-3

A suspension of pyrimidine 116 (0.5 g, 2.27 mmol) in MeOH (25mL) was treated by dropwise addition of a soln of 2,2-diethoxyethylamine(395 muL, 23 mmol) in MeOH (5 mL). Na2CO3 (0.29 g,2.73 mmol) was added and the mixture was stirred at r.t. for 1 h.H2O (100 mL) was then added and the resulting precipitate was collectedby filtration, dried, and crystallized (hexane) to give a colorlesssolid; yield: 0.53 g (74%); mp 74-75 C.IR (KBr): 3332 (NH), 2222 (CN) cm-1.1H NMR (300 MHz, CDCl3): delta = 1.28 (t, J = 6.9 Hz, 6 H, 2 ¡Á CH3),2.56 (s, 3 H, SCH3), 3.60 (dq, 2J = 9.6 Hz, 3J = 6.9 Hz, 2 H,2 ¡Á CHAHBCH3), 3.70-3.84 (m, 4 H, NCH2 and 2 ¡Á CHAHBCH3),4.64 (t, J = 5.4 Hz, 1 H, OCH), 5.89 (t, J = 5.4 Hz, 1 H, NH).13C NMR (75 MHz, CDCl3): delta = 14.7, 15.6, 44.0, 63.5, 86.1, 100.2,113.8, 161.2, 161.5, 176.3.Anal. Calcd for C12H17ClN4O2S: C, 45.49; H, 5.41; found: C, 45.62;H, 5.57.

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, 645-36-3, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Juskenas, Robertas; Masevicius, Viktoras; Tumkevicius, Sigitas; Synthesis; vol. 45; 17; (2013); p. 2438 – 2446;,
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