Month: June 2021

Application of 176317-02-5, A common heterocyclic compound, 176317-02-5, name is 1-Bromo-2,3,4-trifluorobenzene, molecular formula is C6H2BrF3, 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 1: 5-bromo-2,3,4-trifluorobenzoic acid To a solution of 1-bromo-2,3,4-trifluorobenzene (13.64 g, 64.6 mmol) in THF (120 mL) was added lithium diisopropylamide (2.0 M in THF, 33.9 mL, 67.8 mmol) at -78 C. under nitrogen atmosphere. After stirring for 1 h at -78 C., the mixture was transferred to a bottle with dry ice. The mixture was stirred overnight at room temperature. The reaction was quenched with 10% aqueous HCl (300 mL) and extracted with ethyl acetate (200 mL*3). The combined organic extracts were washed with 5% sodium hydroxide (300 mL). The aqueous layer was acidized to pH 1 and extracted with ethyl acetate (200 mL*3). The combined organic extract was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the desired product (white solid, 13.51 g, 82% yield). 1H NMR (400 MHz, CDCl3): delta 13.94 (s, 1H), 7.95 (m, 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; TIANJIN BINJIANG PHARMA, INC.; Tian, Hongqi; Ji, Conghui; Liu, Chunlei; Kong, Li; Cheng, Ying; Huang, Gongchao; US2014/371278; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

61613-22-7, name is 2-Bromo-N-phenylaniline, 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. Formula: C12H10BrN

After dissolving 10 g of 2-bromo-N-phenylphenylamine in 100 ml of tetrahydrofuran, the reaction temperature was lowered to -78 C,Slowly add 20 ml of 2.5 M butyllithium and stir for 1 h. 11 g of benzophenone was dissolved in 100 ml of tetrahydrofuran and slowlyAfter dropping, the temperature was increased to room temperature and stirred for 12 h. After the reaction has ended, distilled water and methylene chloride will be usedRow extraction and drying by anhydrous magnesium sulfate followed by filtration under reduced pressure gave the solid which was dissolved in 100 ml of acetic acid, 7 ml of sulfuric acid was added dropwise and the mixture was reflux-stirred. After the reaction was completed, the mixture was extracted with distilled water and methylene chlorideThe resulting solid was purified by column chromatography to give Intermediate B-1 (7.1 g, yield 53%).

The synthetic route of 61613-22-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Changchun Hai Purunsi Technology Co., Ltd.; Liu Xiqing; Cai Hui; (24 pag.)CN107400085; (2017); A;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 22385-77-9,Some common heterocyclic compound, 22385-77-9, name is 1-Bromo-3,5-di-tert-butylbenzene, molecular formula is C14H21Br, 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.

2,6-Bis(aniline)pyridine (500 mg, 1.914 mmol), 3,5-di-t-butyl-bromobenzene (1.26 g, 4.688 mmol), Pd2(dba)3 (87.6 mg, 95.7 mumol), BINAP (128.7 mg, 229.5 mumol) and sodium t-butoxide (552 mg, 5.744 mmol) were dissolved in 15 mL of toluene. The mixture was stirred for 48 h at 90 0C before cooling it to room temperature and quenching the reaction with 20 mL of water. After separation with dichloromethane, the volatiles were removed in vacuo from the organic extract. The obtained orange oil was passed through a silica gel column by a 20:1 mixture of dichloromethane and ethyl acetate and then was triturated from cold methanol and collected by filtration. 854 mg of pale-yellow solid 6a were obtained after a single wash (70 percent yield). 1H NMR (CDCl3) delta: 1.22 (s, 36eta, C(CH3)3), 6.93 (td, 2eta), 6.99 (t, 2H tBu-Ph-H), 7.05 (d, 4eta, tBu-Ph-H), 7.30 (td, 2eta), 7.54 (dd, 2H), 7.66 (d, 4H, Ph-H, Py-H), 7.90 (t, 1eta, Py-H), 9.8 (s, 2eta,NH). 1H-NMR (C6D6) delta: 1.22 (s, 36H, C(CH3)3), 6.86 (td, 2eta, Ph-H), 7.14 (t, 2eta), 7.1-7.2 (d+t, 3H, Py-H), 7.24 (td, 2eta, Ph-H), 7.32 (d, 4eta), 7.52 (dd, 2H, Ph-H), 7.85 (dd, 2eta, Ph-H), 10.14 (s, 2eta,NH). 13C NMR (CDCl3) delta: 31.6 (CH3), 35.0 (C(CH3)3), 114.6, 115.8, 116.1, 118.9, 120.5, 124.7, 130.0, 130.5, 138.5, 141.5, 143.2, 151.9, 157.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-3,5-di-tert-butylbenzene, its application will become more common.

Reference:
Patent; CALIFORNIA INSTITUTE OF TECHNOLOGY; AGAPIE, Theodor; GOLISZ, Suzanne; TOFAN, Daniel; BERCAW, John, E.; WO2008/36882; (2008); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

These common heterocyclic compound, 348-57-2, name is 1-Bromo-2,4-difluorobenzene, 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. Recommanded Product: 1-Bromo-2,4-difluorobenzene

2,4-difluorobromobenzene (3 g, 15.5 mmol) and 260 mg of iron filings were placed in a two-neck flask, and 15 ml of dichloromethane was then added thereto. The two-neck flask was cooled in an ice bath, and a solution including bromine (1 ml, 18.7 mmol) and 15 ml of dichloromethane was added dropwise to the two-neck flask using an isobaric funnel. Next, the contents in the two-neck flask were heated under reflux for 3 hours. During heating, brown gas was produced. Then, the temperature was reduced to 20 C., and 50 ml of a sodium metabisulfite (Na2S2O5) aqueous solution (10%) was mixed with the contents in the two-neck flask by stirring for 1 hour for terminating the reaction therein. Thereafter, the contents in the two-neck flask were washed several times with deionized water to collect an organic layer, the organic layer was dehydrated using sodium sulfate (Na2SO4), and the solvent in the organic layer was removed, followed by column chromatography (SiO2, n-hexane), thereby obtaining white crystals (3.5 g, 83% yield). (0067) The spectrum analysis for the white crystals is: 1H NMR (400 MHz, CDCl3): delta 7.74 (t, J=7.6 Hz, 1H), 6.96 (t, J=8.0 Hz, 1H); 19F NMR (376 MHz, CDCl3, 298 K): delta -103.8 (dd, J=7.5 Hz, J=7.5 Hz). The white crystals were confirmed to be Compound L3-1 having a chemical structure represented by

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

Reference:
Patent; NATIONAL TSING HUA UNIVERSITY; Chi, Yun; Tong, Bi-Hai; Duan, Tai-Nan; Ku, Hsiao-Yun; Chen, I-Jen; US9219237; (2015); B1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 6320-40-7, These common heterocyclic compound, 6320-40-7, name is 1,3,5-Tribromo-2-methylbenzene, 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.

Synthesizing of Intermediates A and B 3.3g (10 mmol) of 2,4,6-tribromotoluene was dissolved in 30 mL of diethylether. The resulting solution was cooled to -78 C and 4.4mL (11 mmol) of normalbutylithium (2.5M in Hexane) was slowly added thereto. The resulting solution was stirred at -78C for one hour and 1.48g (11 mmol) of cooper chloride (II) was added thereto at -78C. The reactant product was stirred for 5 hours and cleaned using distilled water and ethylacetate at room temperature. The cleaned ethylacetate layer was dried over MgSO4 and dried under a reduced pressure, thereby producing a crude-product. The pre-product was refined through a column chromatography and the refined result was recrylstallized in dichloromethane and hexane, thereby producing white solid intermediates A and B. Amounts of A and B were 622 mg (yield 25%) and 746 mg (yield: 30%), respectively. Intermediate A : 1H NMR (CDCl3, 400MHz) delta (ppm) 7.74 (d, 4H), 7.18 (d, 4H), 2.06 (s, 6H); 13C NMR (CDCl3, 100MHz) delta (ppm) 142.8, 134.9, 134.5, 131.1, 126.4, 119.4, 19.9 Intermediate B : 1H NMR (CDCl3, 400MHz) delta (ppm) 7.60 (s, 4H), 2.61 (s, 6H); 13C NMR (CDCl3, 100MHz) delta (ppm) 138.3, 137.2, 129,9, 125.8, 23.5

The synthetic route of 6320-40-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Samsung SDI Co., Ltd.; EP1752442; (2007); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 59907-13-0, These common heterocyclic compound, 59907-13-0, name is 2-Bromo-1-fluoro-3-methylbenzene, 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.

A 10 mL round-bottomed flask was charged with 2-bromo-l-fluoro-3- methylbenzene (0.13 mL, 0.70 mmol, Sigma-Aldrich, St. Louis, MO) and tetrahydrofuran (2.0 mL). The solution was cooled to -78 C, n-butyllithium (0.28 mL of a 2.5 M solution with hexane, 0.70 mmol, Sigma-Aldrich, St. Louis, MO) was added, and then the reaction mixture was stirred for 30 min. After that time, a solution of N-(l-benzofuran-2-ylmethylidene)-3,4-dihydro-2H-l,5- benzodioxepine-7-sulfonamide (intermediate A) (0.10 g, 0.28 mmol) and tetrahydrofuran (3.0 mL) was added. After stirring for 1 h, water (0.10 mL) was added, and the reaction mixture was warmed to room temperature andconcentrated. The residue was subjected to reversed-phase preparative HPLC (Phenomenex Gemini CI 8 column (Phenomenex, Inc., Torrance, CA)(150 x 30 mm, 5 muiotaeta) eluting with 0.10% trifluroacetic acid in acetonitrile-water, gradient of 10% to 90% over 10 min) to give N-(l-benzofuran-2-yl(2-fluoro-6- methylphenyl)methyl)-3,4-dihydro-2H-l,5-benzodioxepine-7-sulfonamide (0.013 g) as a yellow film (racemic mixture).1H NMR (300 MHz, methanol-d4) delta 7.48 (m, 1 H), 7.36 – 7.30 (m, 2 H), 7.25 – 7.14 (m, 5 H), 6.97 (d, J= 6.0 Hz 1 H), 6.86 (d, J= 9.0 Hz, 1 H), 6.80 (m, 1 H), 6.51 (s, 1 H), 6.11 (s, 1 H), 4.20 – 4.15 (m, 2 H), 4.13 – 4.08 (m, 2 H), 2.41 (s, 3 H), 2.20 – 2.12 (m, 2 H). m/z (ESI, +ve ion) 490.0 (M+Na)+. GK-GKRP EC50 (LCMS/MS) = 0.79 muMu. GK-GKRP IC50 (Binding) = 1.0 muMu.

Statistics shows that 2-Bromo-1-fluoro-3-methylbenzene is playing an increasingly important role. we look forward to future research findings about 59907-13-0.

Reference:
Patent; AMGEN INC.; BARTBERGER, Michael, D.; CROGHAN, Michael, D.; FOTSCH, Christopher, H.; NORMAN, Mark, H.; PENNINGTON, Lewis, D.; REICHELT, Andreas; ST. JEAN, David, J., Jr.; TEGLEY, Christopher, M.; WO2012/138776; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

43204-63-3, name is Bis(2-Bromoethyl)amine hydrobromide, 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. Recommanded Product: 43204-63-3

PREPARATION EXAMPLE 4 (2S)-3-{4-[2-(5-methyl-2-phenyl-1, 3-oxazol-4-yl)-ethoxy]-phenyl}-2-piperazin-1-yl-propionic acid methyl ester (Intermediate 4) Diethanolamine (100 g) and 40% HBr aqueous solution (1000 mL) were mixed and vigorously refluxed for 10 h, while water was removed continuously under reduced pressure during the reaction. The resulting solution was concentrated to give 297 g of a brown liquid. The above brown liquid (47.4 g), Intermediate 3A (4.5 g, 11.8 mmol ) and 150 mL of anhydrous ethanol were mixed with refluxing overnight. Thereafter, the mixture was cooled to room temperature, to which Na2CO3 (1.3 g, 11.8 mmol) was added before further refluxing for 10 h. After cooling to room temperature, the mixture was filtered and evaporated to remove ethanol. The residue was dissolved in CHCl3, and washed with water and saturated brine in turn, and then dried over anhydrous Na2SO4. After concentration and purification with silica gel column chromatography (using CHCl3/CH3OH (60/1) as an eluent), Intermediate 4A (1.0 g, 24% yield) as a brown solid was obtained. MS[M]+=449.4 m/e; 1H-NMR (400 MHz, DMSO-d6), delta 7.987.96 (m, 2H), 7.467.38 (m, 3H), 7.06 (d, 2H), 6.81 (d, 2H), 2.702.61 (m, 2H), 2.602.51 (m, 2H), 2.36 (s, 3H).

The synthetic route of 43204-63-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BEIJING MOLECULE SCIENCE AND TECHNOLOGY CO., LTD.; US2007/259883; (2007); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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 22034-13-5 as follows. Application In Synthesis of 4-Bromobenzo[c][1,2,5]thiadiazole

General procedure: To a solution of 4-bromobenzo[c] [1,2,5]thiadiazole (107 mg,0.50 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (124 mg, 0.50 mmol) in toluene-ethanol(30 mL/10 mL), Pd(PPh3)4 (57 mg, 0.05 mmol) and anhydrous K2CO3 (207 mg, 1.5 mmol) were added under an argon flow at room temperature. The mixturewas then heated to 80 °C for12 h. The mixture was quenched with water after cooling back to room temperature and extracted with dichloromethane. The combined extract was dried with anhydrous Na2SO4 and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with CH2Cl2/petroleum (1:1) to afford NBT as an orange solid.

According to the analysis of related databases, 22034-13-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Jiang, Di; Chen, Songhua; Xue, Zheng; Li, Yongjun; Liu, Huibiao; Yang, Wensheng; Li, Yuliang; Dyes and Pigments; vol. 125; (2016); p. 100 – 105;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 129316-09-2, 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. 129316-09-2, name is 1,3-Dibromo-5-(tert-butyl)benzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Step 1 : Benzyl(3-bromo-5-tert-butylphenyl)sulfane (P21a)1,3-Dibromo-5-te?-butylbenzene (2.89 g, 10 mmol) in dioxane (160 mL) was stirred under Ar. Then DIPEA (3.09 mL, 16 mmol), Xantphos (0.28 g, 0.48 mmol) and Pd2(dba)3 (0.24 g, 0.24 mmol) were added and the reaction was heated to 100C. Phenyl-methanethiol (0.94 mL, 8 mmol) was slowly added and the reaction was stirred for 6 h, quenched by the addition of H20 (15 mL) and extracted with EA (3 x). The combined organic layers were washed with water, dried over Na2S04, filtered, evaporated and purified by CC to afford compound P21a (1.7 g, 72%).

The synthetic route of 1,3-Dibromo-5-(tert-butyl)benzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHENEX PHARMACEUTICALS AG; STEENECK, Christoph; KINZEL, Olaf; GEGE, Christian; KLEYMANN, Gerald; HOFFMANN, Thomas; WO2012/139775; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 38573-88-5, These common heterocyclic compound, 38573-88-5, name is 1-Bromo-2,3-difluorobenzene, 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.

Add slowly a solution of 1-methyl-piperidin-4-ol (2.98 g) in DMF (20 mL) into a suspension of sodium hydride (95percent) (0.72 g) in DMF (25 mL) at room temperature. Heat the mixture in an oil bath at 65°C. After 30 MIN., add 1-bromo-2-, 3-DIFLUORO-BENZENE (5.0 g) and stir at 65°C. After 2 hr. , partition the reaction mixture between water and ether, dry over ANHYDROUS sodium sulfate, and evaporate to give a yellow oil. Separate on a silica gel column (110 g, solvent: ether, ETHER-2M NH3 in methanol 19: 1,9 : 1) to obtain 4- (2-bromo-6-fluoro-phenoxy)-1-methyl-piperidine (4.06 g, 54percent yield) and the title compound (1.60 g, 21percent yield). Mass spectrum (electric spray) M/Z = 288 (M+L), 290 (M+2+1) ;1H NMR (CDC13) : 7.12 (m, 1H), 6.92 (m, 2H), 4.30 (m, 1H), 2.69 (m, 2H), 2.30 (s, 3H), 2.28 (m, 2H), 1.97 (m, 2H), 1. 89 (m, 2H).

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

Reference:
Patent; ELI LILLY AND COMPANY; WO2004/94380; (2004); A1;,
Bromide – Wikipedia,
bromide – Wiktionary