Month: June 2021

Electric Literature of 38573-88-5, A common heterocyclic compound, 38573-88-5, name is 1-Bromo-2,3-difluorobenzene, molecular formula is C6H3BrF2, 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.

Under nitrogen atmosphere, diisopropylamine (5.8 g) was dissolved in THF (30 mL) and cooled to -70 C. or lower. To the solution, a 1.6 M butyllithium / hexane solution (32 mL) was added dropwise at such a rate that the inner temperature did not reach -65 C., and the mixture was subsequently stirred at -70 C. or lower for 30 minutes.Subsequently, a solution prepared by dissolving 2,3-difluorobromobenzene (10 g) in THF (50 mL) was added dropwise to the stirring reaction solution at a rate such that the internal temperature did not exceed -65 C.,The mixture was stirred at -70 C. or lower for 1 hour to prepare phenyllithiums.In a separate reaction vessel, a solution of difluorodibromomethane (16.3 g) dissolved in THF (160 mL) was cooled to -70 C. or lower, and a solution of the phenyllithium prepared in advance was added to the solution in a cannula , Followed by stirring at -70 C. or lower for 1 hour,And the mixture was heated to room temperature.Water and hexane were added to the reaction solution to separate the organic layer, and the organic layer was washed twice with saturated brine.Sodium sulfate was added to the organic layer after washing, dried, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 4-bromo-2,3-difluoro- (bromodifluoromethyl) benzene and 1,4 – dibromo-2,3-difluorobenzene (14.5 g). By measuring the ratio of each compound in the mixture using gas chromatography, 78.5% of 4-bromo-2,3-difluoro- (bromodifluoromethyl) benzene, 1,4-dibromo- 3-Difluorobenzene was 21.5%.

The synthetic route of 38573-88-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DIC CORPORATION; TOJO, KENTA; KUSUMOTO, TETSUO; TAKATSU, HARUYOSHI; (13 pag.)JP6019595; (2016); B2;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 3972-64-3, 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. 3972-64-3, name is 1-Bromo-3-(tert-butyl)benzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Compound 112a. To a solution of 1-bromo-3-(tert-butyl)benzene (0.2 g, 0.938 mmol, 1.0 equiv) in DMSO (10 mL) was added 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (0.356 g, 1.41 mmol, 1.5 equiv), KOAc (0.184 g, 1.876 mmol, 2.0 equiv) and resulting reaction mixture purged with N2 gas for 10 minute, followed by the addition of Pd(PPh3)4 (0.055 g, 0.047 mmol. 0.05 equiv). The resulting reaction mixture was heated at 100 C. for overnight. Product formation was confirmed by LCMS. After the completion of reaction, the mixture was filtered through celite bed, washed with ethyl acetate (100 mL). Filtrate was concentrated under reduced pressure. The crude product obtained was purified by flash chromatography (hexane as an eluent) to obtain 2-(3-(tert-butyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.230 g, 94.26% Yield) as an off-white solid. (0909) LCMS 261.3 [M+H]+ (0910) 1H NMR (400 MHz, DMSO-d6) delta7.67 (s, 1H), 7.57-7.45 (m, 2H), 7.32 (t, J=7.5 Hz, 1H), 1.44 (d, J=6.6 Hz, 1H), 1.39-1.23 (m, 9H), 1.23-1.04 (m, 12H)

The synthetic route of 1-Bromo-3-(tert-butyl)benzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Praxis Biotech LLC; ALFARO, Jennifer; BELMAR, Sebastian; BERNALES, Sebastian; PUJALA, Brahmam; PANPATIL, Dayanand; BHATT, Bhawana; US2019/185451; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

These common heterocyclic compound, 337915-79-4, name is 5-Bromo-N1-methylbenzene-1,2-diamine, 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. Safety of 5-Bromo-N1-methylbenzene-1,2-diamine

[000814j To a stirred solution of compound 1 (0.1 g, 1 eq) in DMF (5 mL),TEA ( 0.101 g, 2 eq) and 4-chlorobutanoyl chloride (0.06 1 g, 1 eq) was added at 0 C and stirred at room temperature for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was evaporated under reduced pressure and the residue was basified using saturated sodium bicarbonate solution and extracted with ethyl acetate (2 X 20 mL). Combined organic extracts were washed with brine and dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was dissolved in acetic acid (5 mL) and was heated to 70 C for 18 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was evaporated under vacuum and residue was basified with saturated sodium bicarbonate solution and extracted with ethyl acetate (2 X 25 mL). Combined organic extracts were washed with brine and dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel 100-200 mesh using 80% EtOAc-hexane to afford the title compound 2. LCMS (mlz): 289.00 (M + 1).

The synthetic route of 5-Bromo-N1-methylbenzene-1,2-diamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOMARIN PHARMACEUTICAL INC.; BHAGWAT, Shripad; WANG, Bing; LUEDTKE, Gregory R.; SPYVEE, Mark; (490 pag.)WO2016/57834; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 74586-53-1, A common heterocyclic compound, 74586-53-1, name is 3-Bromo-5-methylaniline, molecular formula is C7H8BrN, 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.

Example 1.54 N-(3-Bromo-5-methylphenyl)-4-(difluoromethyl)-5-fluoropyrimidin-2-amine 2-Chloro-4-(difluoromethyl)-5-fluoropyrimidine (30 g, 162 mmol, 1.00 equiv) p- TsOH (37 g, 215 mmol, 1.33 equiv), 1,4-dioxane (600 mL), 3-bromo-5-methylaniline (46 g, 247 mmol, 1.53 equiv) were added into a 1000-mL pressure tank reactor purged and maintained with an inert atmosphere of nitrogen. The resulting solution was stirred for 72 h at 105C. The reaction mixture was cooled to room temperature. The solid was filtered out and the filtrate was concentrated under reduced pressure. The residue was applied onto a silica gel and purified column chromatography on silica (1 :20 ethyl acetate/petroleum ether) to afford N-(3-bromo-5- methylphenyl)-4-(difluoromethyl)-5-fluoropyrimidin-2-amine as a yellow solid. MS ESI calc’d. for Ci2H10BrF3 3 [M+H] + 332/334, found 332/334. NMR (400 MHz, CDC13): delta 8.45 (1H, s), 7.73 (1H, s), 7.21 (1H, s), 7.18 (1H, s), 7.05 (1H, s), 6.63 (1 H, t, J = 53.37 Hz), 2.34 (3H, s).

The synthetic route of 74586-53-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MERCK CANADA INC.; MACHACEK, Michele, R.; ALTMAN, Michael, D.; ROMEO, Eric, T.; VITHARANA, Dilrukshi; CASH, Brandon; SIU, Tony; ZHOU, Hua; CHRISTOPHER, Matthew; KATTAR, Solomon, D.; HAIDLE, Andrew, M.; CHILDERS, Kaleen Konrad; MADDESS, Matthew, L.; REUTERSHAN, Michael, H.; DUCHARME, Yves; GUERIN, David. J.; SPENCER, Kerrie; BEAULIEU, Christian; TRUONG, Vouy Linh; GUAY, Daniel; NORTHRUP, Alan, B.; TAOKA, Brandon, M.; LIM, Jongwon; FISCHER, Christian; BUTCHER, John, W.; OTTE, Ryan, D.; SUN, Binyuan; WO2013/192125; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 327-51-5, name is 1,4-Dibromo-2,5-difluorobenzene, A new synthetic method of this compound is introduced below., Recommanded Product: 1,4-Dibromo-2,5-difluorobenzene

n-Butyl lithium (3.6 ml,7.7 mmol) was added drop wise to a solution of 1,4- dibromo-2,5-difluoro-benzene (2g, 7.35mmol) in dry ether at -78C under nitrogen atmosphere and the resulting mixture was stirred at -78C for 30 minutes. This was followed by the addition of DMF (0.85ml, 11.03mmol) in dry THF. The resultant was stirred at room temperature for 1 hour. The reaction was monitored by TLC (5% ethyl acetate in hexane). The reaction mixture was partitioned between ethyl acetate and saturated ammonium chloride. The organic layer was concentrated and purified by column chromatography on silica gel (2% ethyl acetate in hexane) to afford 600mg of the product (37% yield).1H NM (CDC13, 300 MHZ): delta 10.27-10.26 (d, 1H), 7.61-7.57 (t, 1H), 7.49- 7.44 (q, 1H)

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; NOVARTIS AG; BOCK, Mark Gary; GAUL, Christoph; GUMMADI, Venkateshwar Rao; SENGUPTA, Saumitra; WO2012/149413; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 7745-91-7, 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. 7745-91-7, name is 3-Bromo-4-methylaniline belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

57.62 g (0.3 mol, 1 eq) of 3-bromo-4-methylaniline are added to a solution of 75.8 g (0.344 mol, 1.15 eq) of di-tert-butyl dicarbonate in 580 mL of 2N sodium hydroxide solution. The reaction medium is refluxed for one hour and stirred at room temperature for 4 hours. The reaction medium is filtered and the solid is washed with water until the filtrate is neutral, and then dried. 90.33 g of tert-butyl (3-bromo-4-methylphenyl)carbamate are obtained in solid form.Crude yield > 100%

The synthetic route of 3-Bromo-4-methylaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALDERMA RESEARCH & DEVELOPMENT, S.N.C.; WO2006/18326; (2006); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

10016-52-1, name is 2,8-Dibromodibenzo[b,d]furan, belongs to bromides-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. HPLC of Formula: C12H6Br2O

2,8-Dicyanodibenzofuran 11. A mixture of 2,8-dibromodibenzofuran (10, 10.93 g, 33.53 mmol) and copper(I) cyanide (8.91 g, 102 mmol) in DMF (80 mL) was refluxed under N2 for 9 h. The reaction mixture was poured into ice-water (300 mL). The precipitated solid was filtered off and stirred overnight in a solution of ethylenediamine (50 mL) in water (300 mL). The solid was filtered off, washed with water, then stirred in 10% sodium cyanide solution (100 mL) overnight. The solid was further purified by suspension in hot ethanol (100 mL) to give a white powder (6.97 g, 95.2%): mp 298-300 C. (dec.) (Lit. [37] 299 C.); HPLC method 1 tR=24.07 min (97.3 area %); 1H NMR (400 MHz, DMSO-d6) delta 8.05 (d, J=8.7 Hz, 2 H), 8.12 (dd, J1=8.7 Hz, J2=1.4 Hz, 2 H), 8.85 (d, J=1.4 Hz, 2 H). Anal. (C14H6N2O.0.4H2O) C, H, N. 4,4′-Dibromo-2,2′-dinitrobiphenyl 14 [Moffatt, J. S. 3:6-Diamidinodibenzofuran. J. Chem. Soc. 1951, 625-62]. A suspension of 2,5-dibromonitrobenzene (13, 50.0 g, 178 mmol) and copper powder (100 mesh, 25.0 g, 391 mmol) in DMF (300 mL) was stirred at 137 C. (oil bath) under N2 for 2 h. The mixture was poured into toluene (1000 mL) and stirred for 4 h. Then the mixture was passed through Celite 545. The filtrate was collected and washed with water and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was recrystallized from ethanol (650 mL) to give a pale yellow solid (31.33 g, 87.57%): m.p. 143-146 C. (reported 150 C. [Shaw, F. R.; J. Chem. Soc. 1932, 285-297] and 146-148 C. [Yamato, T.; et al., J. Org. Chem. 1991, 56, 6248-6250]); HPLC method 3 tR=18.70 min (97.2%); NMR (300 MHz, CDCl3) delta 8.40 (d, J=2.0 Hz, 2 H), 7.85 (dd, J1=8.2 Hz, J2=2.0 Hz, 2 H), 7.18 (d, J=8.2 Hz, 2 H).

The synthetic route of 10016-52-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The University of North Carolina at Chapel Hill; US6172104; (2001); B2;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 771583-12-1, A common heterocyclic compound, 771583-12-1, name is 2-(Aminomethyl)-4-bromoaniline, molecular formula is C7H9BrN2, 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.

Step 2: 6-bromo-3.4-dihvdroquinazolin-2(1 H)-one; To a solution of triphosgene (0.445 g, 1.5 mmol) in tetrahydrofuran (20 mL) was added triethylamine (0.454 g, 4.5 mmol) dropwise at 0 0C under nitrogen. After stirring for 30 min, a solution of 2-(aminomethyl)-4-bromoaniline (0.201 g, 1 mmol) in tetrahydrofuran (10 mL) was added dropwise. The mixture was allowed to stir for 16 h at room temperature. The mixture was diluted with water (15 mL) and the pH of the resultant mixture was adjusted to 8 – 9 by the addition of 1 M aqueous sodium hydroxide. The mixture was extracted three times with ethyl acetate (30 mL). The combined organic layer was dried over sodium sulfate and concentrated. The residue was purified by re- crystallization from a mixture o dichloromethane and diethyl ether to give the title compound (0.13 g, 57.5%) as a yellow solid. 1 H NMR (400MHz, DMSO-Cf6) delta ppm 9.12 (s, 1 H), 7.29 (S, 1 H), 7.27(d, J = 8.4 Hz, 1 H), 6.87 (s, 1 H), 6.70 (d, J = 8.4 Hz, 1 H), 4.28 (s, 2H).

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; PFIZER INC.; ARHANCET, Graciela Barbieri; CASIMIRO-GARCIA, Agustin; CHEN, Xiangyang; HEPWORTH, David; MEYERS, Marvin Jay; PIOTROWSKI, David Walter; RAHEJA, Raj Kumar; WO2010/116282; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 69321-60-4, name is 2,6-Dibromotoluene, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 2,6-Dibromotoluene

3-Bromo-2-methylbenzonitrile. This compound was prepared in a manner similar to that described for 3-bromo-5-fluorobenzonitrile from commercially available 2,6-dibromotoluene (1.80 g, 7.20 mmol), DMF (11 mL), pyridine (1.1 mL), and copper (I) cyanide (0.52 g, 5.76 mmol). The crude product was purified by flash column chromatography (100 mL silica, hexane) to afford 50 mg (35%) of 3-bromo-2-methylbenzonitrile.

According to the analysis of related databases, 69321-60-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ligand Pharmaceuticals Incorporated; US5688810; (1997); A;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 112734-22-2, name is (4-Bromo-2-fluorophenyl)methanamine belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. category: bromides-buliding-blocks

Step 1: 3-(4-Bromo-2-fluoro-benzyl)-7-methoxy Benzo[e][1,3]oxazine-2,4-dione: A solution of 2-hydroxy-4-methoxybenzoic acid (2.04 g, 12.2 mmol) in tetrahydrofuran (20 mL, 0.6 M) was cooled to 0 C. After being treated with diisopropylethylamine (4.4 mL, 25.3 mmol) and ethyl chloroformate (2.4 mL, 25.1 mmol), the mixture was stirred at room temperature for 1 h and subsequently treater with a solution of 2-fluoro-4-bromobenzylamine (2.92 g, 12.1 mmol) and diisopropylethylamine (4.4 mL, 25.3 mmol) in tetrahydrofuran (15 mL). After stirring at room temperature for 22 h, the reaction mixture was diluted ethyl acetate and successively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The crude solid was purified by recrystallization with heptane and ethyl acetate to give 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) delta 7.87 (d, J=8.4 Hz, 1H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1H), 7.33-7.34 (m, 2H), 7.03-6.99 (m, 2H), 5.02 (s, 2H), 3.87 (s, 3H).

The synthetic route of 112734-22-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Institute for Pharmaceutical Discovery LLC; US6420426; (2002); B1;,
Bromide – Wikipedia,
bromide – Wiktionary