Tag: M.W=200-300

5473-01-8, Name is 2-Bromo-6-methoxyaniline, 5473-01-8, 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.

To a solution of 2-bromo-6-methoxyaniline (AK-90829) (1.000 mL, 7.55 mmol) in tetrahydrofuran (10 mL) was added Pd-PEPPSI-IPent-Cl (dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II), 0.208 g, 0.242 mmol). Nitrogen was bubbled through the solution for about 3 minutes, then a 0.4 M in tetrahydrofuran solution of isopropylzinc(II) bromide (52 mL, 20.80 mmol) was added dropwise over 5 minutes, with nitrogen flushing through the system and the internal temperature rising slowly from 21¡ã C. to 32¡ã C. The reaction mixture was stirred for 15 hours at ambient temperature, at which point it was quenched with saturated aqueous ammonium chloride (50 mL), diluted with methyl tert-butyl ether (400 mL), and the layers were separated. The organic layer was filtered through a pad of silica gel and concentrated in vacuo. The crude material was purified via flash chromatography, eluting on a 40 g silica gel cartridge with 1-40percent ethyl acetate/heptanes over 40 minutes to provide the title compound. 1H NMR (400 MHz, chloroform-d) delta ppm 6.89-6.66 (m, 3H), 3.87 (s, 3H), 3.86 (s, 2H), 2.96 (hept, J=6.8 Hz, 1H), 1.28 (d, J=6.9 Hz, 6H)+

Statistics shows that 2-Bromo-6-methoxyaniline is playing an increasingly important role. we look forward to future research findings about 5473-01-8.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Couty, Sylvain; Desroy, Nicolas; Gfesser, Gregory A.; Housseman, Christopher Gaetan; Kym, Philip R.; Liu, Bo; Mai, Thi Thu Trang; Malagu, Karine Fabienne; Merayo Merayo, Nuria; Picolet, Olivier Laurent; Pizzonero, Mathieu Rafael; Searle, Xenia B.; Van der Plas, Steven Emiel; Wang, Xueqing; Yeung, Ming C.; (189 pag.)US2019/77784; (2019); A1;,
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Adding some certain compound to certain chemical reactions, such as: 74137-36-3, name is 1,3-Dibromo-5-methoxybenzene, 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 74137-36-3. 74137-36-3

To a solution of 1,3-dibromo-5-methoxy-benzene (60 g, 0.2256 mol) and anhydrous Et2O (1 L) cooled to -78 C. and maintained under an Ar atmosphere was added dropwise over 30 min n-BuLi (100 mL, 0.2482 mol, 2.5M in hexane). The yellow solution was stirred at -78 C. for 20 min. To the reaction mixture was added dropwise dry DMF (19 mL, 248.2 mmol) over 15 min and the reaction stirred at -78 C. for 10 min before the cooling bath was removed and the reaction allowed to warm to -30 C. over 30 min. The reaction vessel was placed in an ice-water bath and warmed to -10 C. The mixture was slowly added to an ice cold saturated aqueous NH4Cl solution (400 mL). The organic layer was separated and the aqueous phase thrice extracted with Et2O. The combined extracts were washed with water, dried (MgSO4), filtered and evaporated to afford an oil which solidified on standing. The crude product was purified by SiO2 chromatography eluding with a hexane/EtOAc gradient (3 to 5% EtOAc) to afford 3-bromo-5-methoxy-benzaldehyde.

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 1,3-Dibromo-5-methoxybenzene.

Reference:
Patent; Roche Palo Alto LLC; US2008/249151; (2008); A1;,
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2674-34-2, A common heterocyclic compound, 2674-34-2, name is 1,4-Dibromo-2,5-dimethoxybenzene, molecular formula is C8H8Br2O2, 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.

1,4-Dibromo-2,5-dimethoxybenzene (2.0 g, 6.76 mmol) was added dissolved in THF 35 mL, it was added dropwise a 1.6 M BuLi slowly at -78 . After stirring the reaction solution for 2 hours at -78 , it was added dropwise to DMF (2.8 mL, 33.7 mmol). The reaction solution is stirred at room temperature for 15 hours (20 ). 2 N HCl in a 20 mL reaction mixture was stirred slowly dropping off. The resulting solid was then filtered under reduced pressure, dried to obtain a 2,5-dimethoxyterephthalaldehyde 267 mg (30%).

The synthetic route of 1,4-Dibromo-2,5-dimethoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Korea Research Institute of Chemical Technology; Lee, Jong Chul; Mun, Sang Jin; Sin, Won Suk; Lee, Sang Gyu; (19 pag.)KR101493823; (2015); B1;,
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A common heterocyclic compound, 101-55-3, name is 1-Bromo-4-phenoxybenzene, molecular formula is C12H9BrO, 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. 101-55-3.

EXAMPLE 1 1-(2-Methyl-3-butyn-2-ol)-2-(4-phenyloxyphenyl)ethyne Into a 1 L three-necked, round-bottomed flask equipped with a magnetic stirrer, a condenser, and a nitrogen inlet, 4-bromodiphenylether (50.1 g, 201 mmol), freshly distilled 2-methyl-3-butyn-2-ol (64.3 g, 892 mmol), copper(I) iodide (0.11 g, 0.60 mmol), triphenylphosphine (0.33 g, 1.3 mmol), and bis(triphenylphosphine)palladium(II) chloride (1.12 g, 1.6 mmol) were placed. The solids were carefully washed in with triethylamine (500 mL). The mixture was heated under reflux for 24 h. After the reaction mixture had been allowed to cool to room temperature, the solution was filtered through silica gel. The filtrate was poured into 5% hydrochloric acid solution and diluted with methylene chloride. After separation from the aqueous phase, the organic phase was subjected to purification via a silica-gel column chromatography with methylene chloride/hexane elution to give 40.5 g (80% yield) of light yellow oil. Anal. Calcd. for C17H16O2: C, 80.93%; H, 6.39%; O, 12.68%. Found: C, 80.88%; H, 6.43%; O, 12.89%. Mass spectrum (m/e): 252 (M+, 100% relative abundance).

The synthetic route of 1-Bromo-4-phenoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The United States of America as represented by the Secretary of the Air Force; US6979737; (2005); B1;,
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A common compound: 19056-40-7, name is 4-Bromo-3-methoxyaniline, 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. 19056-40-7

POCl3 (5.07 mL, 54.4 mmol) was added to a mixture of 4-bromo-3- methoxyaniline (10 g, 49.5 mmol) and malonic acid (5.15 g, 49.5 mmol) with thorough mixing, and the mixture was then heated to 105¡ãC. After 5 minutes, the reaction began to bubble vigorously, and eventually formed a hard foam; heating was continued for 1 hour. After cooling, water (200 mL) was added, and the mixture was stirred for 30 minutes. The solid was filtered off and washed with water. 2N NaOH (300 mL) was added to the solid, and stirring was continued overnight. The remaining solid was filtered off; EtOH (5 mL) was then added to the filtrate; and the basic layer was then acidified with concentrated HCl to pH 2. The resulting solid was then filtered off, washed with water. The solid was then transferred to a flask, and the remaining water was removed by stripping off EtOH (200 mL x 2). The solid was then further dried under high vacuum for 15 hours to yield 8.75 g (66percent) of the title compound as an off- white solid. LRMS ESI+ (M+H)+ 270.2/272.2.

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, 19056-40-7, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK & CO., INC.; WO2008/51514; (2008); A2;,
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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. 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below., 450-88-4

Tris-(2-methoxy-4-fluorophenyl)phosphine (L4) preparation. Charge magnesium (Mg) turnings (1.18 g, 48.8 mmol) and five (5) mL THF under nitrogen into a 3-neck round-bottom flask equipped with a reflux condenser and heat the flask contents to 500C with a heating mantle. Add dropwise a solution of 2-bromo-5- fluoroanisol (5.00 g, 24.39 mmol) and 1 ,2-dibromoethane (0.51 g, 2.7 mmol) in THF (total volume of 15 mL) with stirring. Remove the heating mantle five (5) minutes after commencing the addition as the reaction heat becomes sufficient to maintain the reaction temperature. After completing the addition in about 50 minutes to yield a first mixture, reflux the first mixture for an additional 30 minutes to yield a brown solution. After allowing the brown solution to cool to room temperature, separate the brown solution from the unreacted Mg turnings by transferring the brown solution via a cannula into a 100 mL round-bottom flask under nitrogen. Cool the brown solution to -700C and add dropwise a solution Of PCl3 (1.038 g, 7.56 mmol) in seven (7) mL THF with stirring over a period of 30 minutes to yield a second mixture. Heat the second mixture to 500C and stir the second mixture for two (2) hours at 500C. After cooling flask contents to room temperature and transferring the flask into a glovebox, filter the second mixture and wash the filter with diethyl ether (20 mL) to obtain a filtrate. Remove volatiles from the filtrate under vacuum to yield a light brown solid. Dissolve this light brown solid in benzene under an inert nitrogen atmosphere to obtain a benzene solution and wash the benzene solution with deionized water (3 x 20 mL). Dry the organic layer over MgSO4 and then filter it to obtain a dry benzene solution. Remove benzene under vacuum to isolate an off-white solid, which is further purified by recrystallization from acetonitrile (1.60 g, 52.1 % yield). 1H NMR (C6D6): delta 2.99 (s, 3 H), 6.30-6.33 (m, IH), 6.49-6.52 (t of d, 3/HH = 8.2, 2.3, IH), 6.82-6.86 (m, IH). 31P NMR (C6D6, externally referenced using H3PO4): delta -38.9. 19F NMR (C6D6): -110.8 to -110.90 (m, IF).

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; DOW GLOBAL TECHNOLOGIES INC.; BRIGGS, John; PATTON, Jasson; VERMAIRE-LOUW, Sonet; MARGL, Peter; HAGEN, Henk; BEIGZADEH, Daryoosh; WO2010/19360; (2010); A2;,
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75148-49-1, 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. 75148-49-1, name is 3-Bromobenzaldehyde Diethyl Acetal, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: One equiv. of protected hydrazine was dissolved/suspended in EtOH containing 10% water (approx. 5 ml per 1 mmol of protected hydrazine), 1.05 eq of benzaldehyde acetal was added, followed by the addition of 0.05 equiv. of TsOH in an ethanolic solution (10 mg of TsOH per 0.5 ml of EtOH). The obtained reaction mixture was refluxed and monitored by TLC (silica gel) until full conversion of the starting material was observed. Ethyl acetate/light petroleum mixtures or pure ethyl acetate were used as TLC eluents. After completion of the reaction the solvent was removed under reduced pressure, approx. 15 ml of toluene was added to the residue and the solvent was again removed under reduced pressure. The obtained crude hydrazone was dissolved in commercial stabilized THF (approx. 4 ml per 1mmol of hydrazone), the flask was flushed with argon and 3 equiv. of 1M BH3-THF complex was added at room temperature, followed by 3 hours of stirring. The progress of the reaction was checked by TLC and if some unreacted hydrazone was left, stirring was continued for an additional 45 min. After thefull conversion of hydrazone EtOH (10 ml) was added to the reaction mixture (Caution: Liberation of hydrogen) and the obtained mixture was refluxed for 1 hour. After cooling to room temperature the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution, water and saturated NaCl solution. The aqueous phase was extracted twice with ethyl acetate, the extracts were washed with saturated NaCl solution, combined with the organic phase, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel by using ethyl acetate/light petroleum 1:1 or 1:2 mixtures or pure ethyl acetate as eluent. For the exact information about the eluent used for monitoring reaction progress and chromatographic purifications, see the Rf value for each compound.

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; Mastitski, Anton; Niinepuu, Siret; Haljasorg, Toiv; Jaerv, Jaak; Organic Preparations and Procedures International; vol. 50; 4; (2018); p. 416 – 423;,
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2859-78-1, A common heterocyclic compound, 2859-78-1, name is 4-Bromo-1,2-dimethoxybenzene, molecular formula is C8H9BrO2, 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.

METHOD AThe synthesis of (i?)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine.HCl is a representative example of the general two step method of making secondary amine building blocks of the type (V) using a palladium coupling reaction. (R)-tert-bntyl 4-(3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate Palladium(II) acetate (0.052 g, 0.230 mmol) and (R)-(+)-2,2′-bis(diphenylphosphino)-l,l?- binaphthyl (0.115 g, 0.180 mmol) were added to 4-bromoveratrole (0.662 mL, 4.61 mmol), (R)–N-boc-2 -methyl piperazine (0.923 g, 4.61 mmol) and sodium tert-butoxide (0.664 g, 6.91 mmol) in anhydrous toluene (12 mL) under argon. The resulting solution was stirred at reflux for 16 hours. The reaction mixture was diluted with Et2O and filtered through celite. The resulting mixture was evaporated to dryness to afford crude (R)-tert-butyl 4- (3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate. The crude product was purified by flash silica chromatography, elution gradient 0 to 25% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(3,4-dimethoxyphenyl)-2- methylpiperazine-1-carboxylate (0.871 g, 56.2 %) as a beige solid. MS (+ve ESI) : Rt = 2.57 min, 337.31 (M+H)+1H NMi? (400.132 MHz, CDC13) delta 1.33 (3H, d), 1.49 (9H, s), 2.67 (IH, m), 2.85 (IH, m), 3.24 (2H, m), 3.37 (IH, d), 3.84 (3H, s), 3.88 (3H, s), 3.94 (IH, m), 4.34 (IH, s), 6.43 (IH, m), 6.54 (IH, d), 6.79 (IH, d)(R)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine.HCl(R)-tert-buty{ 4-(3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate (0.400 g, 1.19 mmol) was added to hydrochloric acid in methanol (methanol reagent 10) (15 mL, 1.19 mmol) and the resulting solution was stirred at room temperature for 16 hours. The resulting mixture was evaporated to dryness and the residue was azeotroped with DCM to afford crude (i?)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine (100 %). MS (+ve ESI) : Rt = 1.22 min, 237.30 (M+H)+

The synthetic route of 2859-78-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/1127; (2008); A1;,
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1462-37-9,Some common heterocyclic compound, 1462-37-9, name is ((2-Bromoethoxy)methyl)benzene, molecular formula is C9H11BrO, 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.

Step 1. 4-(l-(2-(Benzyloxy)ethyl)-4-(trifluoromethyl)-lH-imidazol-2-yl)benzonitrile (0931) [00299] A mixture of Intermediate B-20 (1 g, 4.22 mmol), ((2-bromoethoxy)methyl)benzene (1.09 g, 5.07 mmol) and cesium carbonate (2.75 g, 8.44 mmol) in DMF (15 mL) was stirred for 18 h at 110 ¡ãC. After cooling to ambient temperature, the reaction mixture was poured into water (100 mL) and was then extracted with EtOAc (2 x 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to afford 1.5 g (96percent) of 4-(l-(2-(benzyloxy)ethyl)-4-(trifluoromethyl)-lH-imidazol-2- yl)benzonitrile as a colorless oil. MS (ESI) m/z 371.8 [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 ((2-Bromoethoxy)methyl)benzene, its application will become more common.

Reference:
Patent; FORMA THERAPEUTICS, INC.; BUCKMELTER, Alexandre Joseph; IOANNIDIS, Stephanos; FOLLOWS, Bruce; GUSTAFSON, Gary; WANG, Minghua; CARAVELLA, Justin A.; WANG, Zhongguo; FRITZEN, Edward L.; LIN, Jian; (414 pag.)WO2017/87837; (2017); A1;,
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These common heterocyclic compound, 105529-58-6, name is 4-Bromo-2-fluoro-1-(trifluoromethoxy)benzene, 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. 105529-58-6

(Fifth stage) In 80 ml of THF was dissolved 8.0 g (30 mmol) of the 2-(3,5-difluorophenyl)-5-pentylpyrimidine described above, and cooled down to -60 C. under nitrogen gas atmosphere. To this solution was added dropwise 20 ml of 1.60 M solution of n-butyl lithium (32 mmol) in hexane while maintaining the condition that the temperature of the solution did not exceed -50 C., and then stirred at the same temperature for 1 hour. Subsequently, 64 ml of 0.5 M solution of zinc chloride (32 mmol) in THF was added dropwise to the reaction solution while maintaining the condition that the temperature of the solution did not exceed -50 C., warmed up to room temperature, and then stirred for 30 min. To this solution were added 0.5 g of tetrakistriphenylphosphine palladium and 8.3 g of 3-fluoro-4-trifluoromethoxybromobenzene, and heated to reflux for 3 hours. To the reaction solution was added 100 ml of water, and the product was extracted with toluene. The extract was washed with 3N-hydrochloric acid, saturated aqueous solution of sodium bicarbonate, and saturated aqueous solution of sodium chloride in turn, and dried over anhydrous magnesium sulfate. The solvent was distilled off. The residue was purified by silica gel column chromatography (eluent: heptane/toluene=1/1), and then recrystallized twice from heptane/ethyl acetate=1/1 to obtain 0.09 g (0.2 mmol) of 2-(4-(3-fluoro-4-trifluoromethoxyphenyl)-3,5-difluorophenyl)-5-pentylpyrimidine. Yield of this product from 2-(3,5-difluorophenyl)-5-pentylpyrimidine was 0.7%.

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 105529-58-6.

Reference:
Patent; Chisso Corporation; US6326065; (2001); B1;,
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